Skip to main content
SpringerLink
Log in

RNA-Binding Proteins in Heart Development

  • Chapter
  • First Online:
Systems Biology of RNA Binding Proteins

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 825))

Abstract

RNA-binding proteins (RBPs) are key players of posttranscriptional regulation occurring during normal tissue development. All tissues examined thus far have revealed the importance of RBPs in the regulation of complex networks involved in organ morphogenesis, maturation, and function. They are responsible for controlling tissue-specific gene expression by regulating alternative splicing, mRNA stability, translation, and poly-adenylation. The heart is the first organ form during embryonic development and is also the first to acquire functionality. Numerous remodeling processes take place during late cardiac development since fetal heart first adapts to birth and then undergoes a transition to adult functionality. This physiological remodeling involves transcriptional and posttranscriptional networks that are regulated by RBPs. Disruption of the normal regulatory networks has been shown to cause cardiomyopathy in humans and animal models. Here we review the complexity of late heart development and the current information regarding how RBPs control aspects of postnatal heart development. We also review how activities of RBPs are modulated adding complexity to the regulation of developmental networks.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AS:

Alternative splicing

CELF1:

CUGBP, ELAV-like family 1

CF:

Cardiac fibroblasts

CLIP-seq:

Cross-linking/immunoprecipitation/sequencing

CM:

Cardiomyocytes

cycD1:

Cyclin D1

cycD3-cdk4:

Cyclin D3-cdk4

DCM:

Dilated cardiomyopathy

DM:

Myotonic distrophy

DM1:

Myotonic dystrophy type 1

DM2:

Myotonic dystrophy type 2

ECC:

Excitation-contraction coupling

eIF2α:

Eukaryotic translation initiation factor 2α

eIF4E:

Eukaryotic translation initiation factor 4E

HDAC:

Histone deacetylase

Hsp32:

Heat-shock protein 32

MBNL:

Muscleblind-like proteins

miRNA:

MicroRNA

nPTB:

Neuronal homolog of PTB

NXF1:

Nuclear export factor 1

PN:

Postnatal day

PTB:

Polypyrimidine tract-binding protein

PEVK:

Titin region rich in proline, glutamate, valine, and lysine

PKC:

Protein kinase C

PKR:

RNA protein kinase

QKI:

Quaking RBP

RBM:

RNA-binding motif protein

RBPs:

RNA-binding proteins

RISC:

RNA-induced silencing complex

RNA-seq:

RNA sequencing

RRM:

RNA recognition motif region

S:

Serine

Sam68:

Src-associated substrate in mitosis of 68 kDa

SR:

Serine/arginine-rich protein

SRSF:

Serine/arginine-rich splicing factor

T:

Threonine

UTR:

Untranslated region

References

  • Adereth Y, Dammai V, Kose N, Li R, Hsu T (2005) RNA-dependent integrin alpha3 protein localization regulated by the Muscleblind-like protein MLP1. Nat Cell Biol 7:1240–1247

    PubMed Central  PubMed  Google Scholar 

  • Ames EG, Lawson MJ, Mackey AJ, Holmes JW (2013) Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy. J Mol Cell Cardiol 62:99–107

    CAS  PubMed Central  PubMed  Google Scholar 

  • Artero R, Prokop A, Paricio N, Begemann G, Pueyo I, Mlodzik M, Perez-Alonso M, Baylies MK (1998) The muscleblind gene participates in the organization of Z-bands and epidermal attachments of Drosophila muscles and is regulated by Dmef2. Dev Biol 195:131–143

    CAS  PubMed  Google Scholar 

  • Auweter SD, Fasan R, Reymond L, Underwood JG, Black DL, Pitsch S, Allain FH (2006) Molecular basis of RNA recognition by the human alternative splicing factor Fox-1. EMBO J 25:163–173

    CAS  PubMed Central  PubMed  Google Scholar 

  • Balza RO Jr, Misra RP (2006) Role of the serum response factor in regulating contractile apparatus gene expression and sarcomeric integrity in cardiomyocytes. J Biol Chem 281:6498–6510

    CAS  PubMed  Google Scholar 

  • Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (2001) The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ Res 89:1065–1072

    CAS  PubMed  Google Scholar 

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baudino TA, Carver W, Giles W, Borg TK (2006) Cardiac fibroblasts: friend or foe? Am J Physiol Heart Circ Physiol 291:H1015–H1026

    CAS  PubMed  Google Scholar 

  • Baulac S, Huberfeld G, Gourfinkel-An I, Mitropoulou G, Beranger A, Prud’homme JF, Baulac M, Brice A, Bruzzone R, LeGuern E (2001) First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Nat Genet 28:46–48

    CAS  PubMed  Google Scholar 

  • Bayer KU, Schulman H (2001) Regulation of signal transduction by protein targeting: the case for CaMKII. Biochem Biophys Res Commun 289:917–923

    CAS  PubMed  Google Scholar 

  • Begemann G, Paricio N, Artero R, Kiss I, Pérez-Alonso M, Mlodzik M (1997) Muscleblind, a gene required for photoreceptor differentiation in Drosophila, encodes novel nuclear Cys3His-type zinc-finger-containing proteins. Development 124:4321–4331

    CAS  PubMed  Google Scholar 

  • Beisang D, Rattenbacher B, Vlasova-St Louis IA, Bohjanen PR (2012) Regulation of CUG-binding protein 1 (CUGBP1) binding to target transcripts upon T cell activation. J Biol Chem 287:950–960

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bhalla K, Phillips HA, Crawford J, McKenzie OL, Mulley JC, Eyre H, Gardner AE, Kremmidiotis G, Callen DF (2004) The de novo chromosome 16 translocations of two patients with abnormal phenotypes (mental retardation and epilepsy) disrupt the A2BP1 gene. J Hum Genet 49:308–311

    PubMed  Google Scholar 

  • Bhakta D, Lowe MR, Groh WJ (2004) Prevalence of structural cardiac abnormalities in patients with myotonic dystrophy type I. Am Heart J 147:224–227

    PubMed  Google Scholar 

  • Bland CS, Wang ET, Vu A, David MP, Castle JC, Johnson JM, Burge CB, Cooper TA (2010) Global regulation of alternative splicing during myogenic differentiation. Nucleic Acids Res 38:7651–7664

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blencowe BJ (2006) Alternative splicing: new insights from global analyses. Cell 126:37–47

    CAS  PubMed  Google Scholar 

  • Boutz PL, Chawla G, Stoilov P, Black DL (2007a) MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev 21:71–84

    CAS  PubMed Central  PubMed  Google Scholar 

  • Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M Jr, Black DL (2007b) A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev 21:1636–1652

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brauch KM, Karst ML, Herron KJ, de Andrade M, Pellikka PA, Rodeheffer RJ, Michels VV, Olson TM (2009) Mutations in ribonucleic acid binding protein gene cause familial dilated cardiomyopathy. J Am Coll Cardiol 54:930–941

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brudno M, Gelfand MS, Spengler S, Zorn M, Dubchak I, Conboy JG (2001) Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing. Nucleic Acids Res 29:2338–2348

    CAS  PubMed Central  PubMed  Google Scholar 

  • Buratti E, Baralle FE (2012) TDP-43: gumming up neurons through protein-protein and protein-RNA interactions. Trends Biochem Sci 37:237–247

    CAS  PubMed  Google Scholar 

  • Busà R, Paronetto MP, Farini D, Pierantozzi E, Botti F, Angelini DF, Attisani F, Vespasiani G, Sette C (2007) The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells. Oncogene 26:4372–4382

    PubMed  Google Scholar 

  • Camelliti P, Borg TK, Kohl P (2005) Structural and functional characterisation of cardiac fibroblasts. Cardiovasc Res 65:40–51

    CAS  PubMed  Google Scholar 

  • Cao X, Wang J, Wang Z, Du J, Yuan X, Huang W, Meng J, Gu H, Nie Y, Ji B, Hu S, Zheng Z (2013) MicroRNA profiling during rat ventricular maturation: A role for miR-29a in regulating cardiomyocyte cell cycle re-entry. FEBS Lett 587:1548–1555

    CAS  PubMed  Google Scholar 

  • Castle JC, Zhang C, Shah JK, Kulkarni AV, Kalsotra A, Cooper TA, Johnson JM (2008) Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines. Nat Genet 40:1416–1425

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chamberlain CM, Ranum LP (2012) Mouse model of muscleblind-like 1 overexpression: skeletal muscle effects and therapeutic promise. Hum Mol Genet 21:4645–4654

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chan RC, Black DL (1995) Conserved intron elements repress splicing of a neuron-specific c-src exon in vitro. Mol Cell Biol 15:6377–6385

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chang S, McKinsey TA, Zhang CL, Richardson JA, Hill JA, Olson EN (2004) Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development. Mol Cell Biol 24:8467–8476

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chang SH, Hla T (2011) Gene regulation by RNA binding proteins and microRNAs in angiogenesis. Trends Mol Med 17:650–658

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chang SH, Lu YC, Li X, Hsieh WY, Xiong Y, Ghosh M, Evans T, Elemento O, Hla T (2013) Antagonistic function of the RNA-binding protein HuR and miR-200b in post-transcriptional regulation of vascular endothelial growth factor-A expression and angiogenesis. J Biol Chem 288(7):4908–4921

    CAS  PubMed Central  PubMed  Google Scholar 

  • Charizanis K, Lee KY, Batra R, Goodwin M, Zhang C, Yuan Y, Shiue L, Cline M, Scotti MM, Xia G et al (2012) Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy. Neuron 75:437–450

    CAS  PubMed Central  PubMed  Google Scholar 

  • Charlet BN, Savkur RS, Singh G, Philips AV, Grice EA, Cooper TA (2002) Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell 10:45–53

    Google Scholar 

  • Chen CM, Chiang SY, Yeh NH (1991) Increased stability of nucleolin in proliferating cells by inhibition of its self-cleaving activity. J Biol Chem 266:7754–7758

    CAS  PubMed  Google Scholar 

  • Chen YH, Huang FL, Cheng YC, Wu CJ, Yang CN, Tsay HJ (2008a) Knockdown of zebrafish Nav1.6 sodium channel impairs embryonic locomotor activities. J Biomed Sci 15:69–78

    CAS  PubMed  Google Scholar 

  • Chen JF, Murchison EP, Tang R, Callis TE, Tatsuguchi M, Deng Z, Rojas M, Hammond SM, Schneider MD, Selzman CH et al (2008b) Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc Natl Acad Sci U S A 105:2111–2116

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen M, Manley JL (2009) Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Biol 10:741–754

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chénard CA, Richard S (2008) New implications for the QUAKING RNA binding protein in human disease. J Neurosci Res 86:233–242

    PubMed  Google Scholar 

  • Cheng H, Zheng M, Peter AK, Kimura K, Li X, Ouyang K, Shen T, Cui L, Frank D, Dalton ND et al (2011) Selective deletion of long but not short Cypher isoforms leads to late-onset dilated cardiomyopathy. Hum Mol Genet 20:1751–1762

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cooper TA, Wan L, Dreyfuss G (2009) RNA and disease. Cell 136(4):777–793

    CAS  PubMed Central  PubMed  Google Scholar 

  • da Costa Martins PA, Bourajjaj M, Gladka M, Kortland M, van Oort RJ, Pinto YM, Molkentin JD, De Windt LJ (2008) Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling. Circulation 118:1567–1576

    PubMed  Google Scholar 

  • Daoud R, Mies G, Smialowska A, Oláh L, Hossmann KA, Stamm S (2002) Ischemia induces a translocation of the splicing factor tra2-beta 1 and changes alternative splicing patterns in the brain. J Neurosci 22:5889–5899

    CAS  PubMed  Google Scholar 

  • Das D, Clark TA, Schweitzer A, Yamamoto M, Marr H, Arribere J, Minovitsky S, Poliakov A, Dubchak I, Blume JE, Conboy JG (2007) A correlation with exon expression approach to identify cis-regulatory elements for tissue-specific alternative splicing. Nucleic Acids Res 35:4845–4857

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dasgupta T, Ladd AN (2012) The importance of CELF control: molecular and biological roles of the CUG-BP, Elav-like family of RNA-binding proteins. Wiley Interdiscip Rev RNA 3:104–121

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dasgupta T, Stillwagon SJ, Ladd AN (2013) Gene expression analyses implicate an alternative splicing program in regulating contractile gene expression and serum response factor activity in mice. PLoS One 8:e56590. doi:10.1371/journal.pone.0056590

  • Davis FJ, Gupta M, Pogwizd SM, Bacha E, Jeevanandam V, Gupta MP (2002) Increased expression of alternatively spliced dominant-negative isoform of SRF in human failing hearts. Am J Physiol Heart Circ Physiol 282:H1521–H1533

    CAS  PubMed  Google Scholar 

  • Ding JH, Xu X, Yang D, Chu PH, Dalton ND, Ye Z, Yeakley JM, Cheng H, Xiao RP, Ross J et al (2004) Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart. EMBO J 23:885–896

    CAS  PubMed Central  PubMed  Google Scholar 

  • Du H, Cline MS, Osborne RJ, Tuttle DL, Clark TA, Donohue JP, Hall MP, Shiue L, Swanson MS, Thornton CA, Ares M Jr (2010) Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy. Nat Struct Mol Biol 17:187–193

    CAS  PubMed Central  PubMed  Google Scholar 

  • Eulalio A, Huntzinger E, Izaurralde E (2008) Getting to the root of miRNA-mediated gene silencing. Cell 132:9–14

    CAS  PubMed  Google Scholar 

  • Fabian MR, Sonenberg N (2012) The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 19:586–593

    CAS  PubMed  Google Scholar 

  • Fardaei M, Rogers MT, Thorpe HM, Larkin K, Hamshere MG, Harper PS, Brook JD (2002) Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells. Hum Mol Genet 11:805–814

    CAS  PubMed  Google Scholar 

  • Faustino N, Cooper T (2005) Identification of putative new splicing targets for ETR-3 using its SELEX sequences. Mol Cell Biol 25:879–887

    CAS  PubMed Central  PubMed  Google Scholar 

  • Feng Y, Chen M, Manley JL (2008) Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator. Nat Struct Mol Biol 15:1040–1048

    CAS  PubMed Central  PubMed  Google Scholar 

  • Feng Y, Valley MT, Lazar J, Yang AL, Bronson RT, Firestein S, Coetzee WA, Manley JL (2009) SRp38 regulates alternative splicing and is required for Ca(2+) handling in the embryonic heart. Dev Cell 16:528–538

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fischer U, Jänicke RU, Schulze-Osthoff K (2003) Many cuts to ruin: a comprehensive update of caspase substrates. Cell Death Differ 10:76–100

    CAS  PubMed  Google Scholar 

  • Fugier C, Klein AF, Hammer C, Vassilopoulos S, Ivarsson Y, Toussaint A, Tosch V, Vignaud A, Ferry A, Messaddeq N, Kokunai Y, Tsuburaya R, de la Grange P, Dembele D, Francois V, Precigout G, Boulade-Ladame C, Hummel MC, Lopez de Munain A, Sergeant N, Laquerrière A, Thibault C, Deryckere F, Auboeuf D, Garcia L, Zimmermann P, Udd B, Schoser B, Takahashi MP, Nishino I, Bassez G, Laporte J, Furling D, Charlet-Berguerand N (2011) Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. Nat Med 17:720–725

    Google Scholar 

  • Gabut M, Chaudhry S, Blencowe BJ (2008) SnapShot: the splicing regulatory machinery. Cell 133:192, e1

    CAS  PubMed  Google Scholar 

  • Gallagher TL, Arribere JA, Geurts PA, Exner CR, McDonald KL, Dill KK, Marr HL, Adkar SS, Garnett AT, Amacher SL, Conboy JG (2011) Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions. Dev Biol 359:251–261

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ge Y, Sun Y, Chen J (2011) IGF-II is regulated by microRNA-125b in skeletal myogenesis. J Cell Biol 192:69–81

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gerber WV, Yatskievych TA, Antin PB, Correia KM, Conlon RA, Krieg PA (1999) The RNA-binding protein gene, hermes, is expressed at high levels in the developing heart. Mech Dev 80:77–86

    CAS  PubMed  Google Scholar 

  • Gerber WV, Vokes SA, Zearfoss NR, Krieg PA (2002) A role for the RNA-binding protein, hermes, in the regulation of heart development. Dev Biol 247:116–126

    CAS  PubMed  Google Scholar 

  • Gesteland RF, Cech TR, Atkins JF (eds) (1999) The RNA World, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

    Google Scholar 

  • Glisovic T, Bachorik JL, Yong J, Dreyfuss G (2008) RNA-binding proteins and post-transcriptional gene regulation. FEBS Lett 582:1977–1986

    CAS  PubMed Central  PubMed  Google Scholar 

  • Goers ES, Purcell J, Voelker RB, Gates DP, Berglund JA (2010) MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing. Nucleic Acids Res 38:2467–2484

    CAS  PubMed Central  PubMed  Google Scholar 

  • Good PJ, Chen Q, Warner SJ, Herring DC (2000) A family of human RNA-binding proteins related to the Drosophila Bruno translational regulator. J Biol Chem 275:28583–28592

    CAS  PubMed  Google Scholar 

  • Graindorge A, Le Tonquèze O, Thuret R, Pollet N, Osborne HB, Audic Y (2008) Identification of CUG-BP1/EDEN-BP target mRNAs in Xenopus tropicalis. Nucleic Acids Res 36:1861–1870

    CAS  PubMed Central  PubMed  Google Scholar 

  • Graveley BR (2000) Sorting out the complexity of SR protein functions. RNA 6:1197–1211

    CAS  PubMed Central  PubMed  Google Scholar 

  • Greaser ML, Warren CM, Esbona K, Guo W, Duan Y, Parrish AM, Krzesinski PR, Norman HS, Dunning S, Fitzsimons DP, Moss RL (2008) Mutation that dramatically alters rat titin isoform expression and cardiomyocyte passive tension. J Mol Cell Cardiol 44:983–991

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gregorio CC, Trombitás K, Centner T, Kolmerer B, Stier G, Kunke K, Suzuki K, Obermayr F, Herrmann B, Granzier H et al (1998) The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. J Cell Biol 143:1013–1027

    CAS  PubMed Central  PubMed  Google Scholar 

  • Groh WJ, Groh MR, Saha C, Kincaid JC, Simmons Z, Ciafaloni E, Pourmand R, Otten RF, Bhakta D, Nair GV et al (2008) Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1. N Engl J Med 358:2688–2697

    CAS  PubMed  Google Scholar 

  • Guo W, Schafer S, Greaser ML, Radke MH, Liss M, Govindarajan T, Maatz H, Schulz H, Li S, Parrish AM et al (2012) RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing. Nat Med 18:766–773

    CAS  PubMed Central  PubMed  Google Scholar 

  • Habelhah H, Shah K, Huang L, Ostareck-Lederer A, Burlingame AL, Shokat KM, Hentze MW, Ronai Z (2001) ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation. Nat Cell Biol 3:325–330

    CAS  PubMed  Google Scholar 

  • Hanson KA, Kim SH, Tibbetts RS (2012) RNA-binding proteins in neurodegenerative disease: TDP-43 and beyond. Wiley Interdiscip Rev RNA 3:265–285

    CAS  PubMed Central  PubMed  Google Scholar 

  • Harper PS (2001) Myotonic dystrophy. WB Saunders, London

    Google Scholar 

  • Hein S, Arnon E, Kostin S, Schönburg M, Elsässer A, Polyakova V, Bauer EP, Klövekorn WP, Schaper J (2003) Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation 107:984–991

    PubMed  Google Scholar 

  • Ho TH, Charlet-B N, Poulos MG, Singh G, Swanson MS, Cooper TA (2004) Muscleblind proteins regulate alternative splicing. EMBO J 23:3103–3112

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ho TH, Bundman D, Armstrong DL, Cooper TA (2005) Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in myotonic dystrophy. Hum Mol Genet 14:1539–1547

    CAS  PubMed  Google Scholar 

  • Holcik M, Sonenberg N (2005) Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 6:318–327

    CAS  PubMed  Google Scholar 

  • Huang C, Zhou Q, Liang P, Hollander MS, Sheikh F, Li X, Greaser M, Shelton GD, Evans S, Chen J (2003) Characterization and in vivo functional analysis of splice variants of cypher. J Biol Chem 278:7360–7365

    CAS  PubMed  Google Scholar 

  • Huang Y, Steitz JA (2001) Splicing factors SRp20 and 9G8 promote the nucleocytoplasmic export of mRNA. Mol Cell 7:899–905

    CAS  PubMed  Google Scholar 

  • Huang Y, Yario TA, Steitz JA (2004) A molecular link between SR protein dephosphorylation and mRNA export. Proc Natl Acad Sci U S A 101:9666–9670

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huang CJ, Tang Z, Lin RJ, Tucker PW (2007) Phosphorylation by SR kinases regulates the binding of PTB-associated splicing factor (PSF) to the pre-mRNA polypyrimidine tract. FEBS Lett 581:223–232

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huichalaf C, Sakai K, Jin B, Jones K, Wang GL, Schoser B, Schneider-Gold C, Sarkar P, Pereira-Smith OM, Timchenko N, Timchenko L (2010) Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1) cells. FASEB J 24:3706–3719

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huot ME, Bisson N, Davidovic L, Mazroui R, Labelle Y, Moss T, Khandjian EW (2005) The RNA-binding protein fragile X-related 1 regulates somite formation in Xenopus laevis. Mol Biol Cell 16:4350–4361

    CAS  PubMed Central  PubMed  Google Scholar 

  • Iakova P, Wang GL, Timchenko L, Michalak M, Pereira-Smith OM, Smith JR, Timchenko NA (2004) Competition of CUGBP1 and calreticulin for the regulation of p21 translation determines cell fate. EMBO J 23:406–417

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ikeda S, Pu WT (2010) Expression and function of microRNAs in heart disease. Curr Drug Targets 11:913–925

    CAS  PubMed  Google Scholar 

  • Ikezoe K, Nakamori M, Furuya H, Arahata H, Kanemoto S, Kimura T, Imaizumi K, Takahashi MP, Sakoda S, Fujii N, Kira J (2007) Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle. Acta Neuropathol 114:527–535

    CAS  PubMed  Google Scholar 

  • Jensen KB, Dredge BK, Stefani G, Zhong R, Buckanovich RJ, Okano HJ, Yang YY, Darnell RB (2000) Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 25:359–371

    CAS  PubMed  Google Scholar 

  • Ji X, Zhou Y, Pandit S, Huang J, Li H, Lin CY, Xiao R, Burge CB, Fu XD (2013) SR proteins collaborate with 7SK and promoter-associated nascent RNA to release paused polymerase. Cell 153:855–868

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jiang B, Zhang B, Liang P, Chen G, Zhou B, Lv C, Tu Z, Xiao X (2013) Nucleolin protects the heart from ischaemia-reperfusion injury by up-regulating heat shock protein 32. Cardiovasc Res 99:92–101

    CAS  PubMed  Google Scholar 

  • Jin Y, Suzuki H, Maegawa S, Endo H, Sugano S, Hashimoto K, Yasuda K, Inoue K (2003) A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG. EMBO J 22:905–912

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jin D, Hidaka K, Shirai M, Morisaki T (2010) RNA-binding motif protein 24 regulates myogenin expression and promotes myogenic differentiation. Genes Cells 15:1158–1167

    CAS  PubMed  Google Scholar 

  • Jumaa H, Wei G, Nielsen PJ (1999) Blastocyst formation is blocked in mouse embryos lacking the splicing factor SRp20. Curr Biol 9:899–902

    CAS  PubMed  Google Scholar 

  • Kakkar R, Lee RT (2010) Intramyocardial fibroblast myocyte communication. Circ Res 106:47–57

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kalsotra A, Xiao X, Ward AJ, Castle JC, Johnson JM, Burge CB, Cooper TA (2008) A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart. Proc Natl Acad Sci U S A 105:20333–20338

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kalsotra A, Wang K, Li PF, Cooper TA (2010) MicroRNAs coordinate an alternative splicing network during mouse postnatal heart development. Genes Dev 24:653–658

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kameyama T, Suzuki H, Mayeda A (2012) Re-splicing of mature mRNA in cancer cells promotes activation of distant weak alternative splice sites. Nucleic Acids Res 40:7896–7906

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kanadia RN, Urbinati CR, Crusselle VJ, Luo D, Lee YJ, Harrison JK, Oh SP, Swanson MS (2003a) Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3. Gene Expr Patterns 3:459–462

    CAS  PubMed  Google Scholar 

  • Kanadia RN, Johnstone KA, Mankodi A, Lungu C, Thornton CA, Esson D, Timmers AM, Hauswirth WW, Swanson MS (2003b) A muscleblind knockout model for myotonic dystrophy. Science 302:1978–1980

    CAS  PubMed  Google Scholar 

  • Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR (2007) The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 14:185–193

    CAS  PubMed  Google Scholar 

  • Kaynak B, von Heydebreck A, Mebus S, Seelow D, Hennig S, Vogel J, Sperling HP, Pregla R, Alexi-Meskishvili V, Hetzer R et al (2003) Genome-wide array analysis of normal and malformed human hearts. Circulation 107:2467–2474

    PubMed  Google Scholar 

  • Keppetipola N, Sharma S, Li Q, Black DL (2012) Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Crit Rev Biochem Mol Biol 47:360–378

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kiehl TR, Shibata H, Vo T, Huynh DP, Pulst SM (2001) Identification and expression of a mouse ortholog of A2BP1. Mamm Genome 12:595–601

    CAS  PubMed  Google Scholar 

  • Kim KK, Adelstein RS, Kawamoto S (2009) Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors. J Biol Chem 284:31052–31061

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kong SW, Hu YW, Ho JW, Ikeda S, Polster S, John R, Hall JL, Bisping E, Pieske B, dos Remedios CG, Pu WT (2010) Heart failure-associated changes in RNA splicing of sarcomere genes. Circ Cardiovasc Genet 3:138–146

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koshelev M, Sarma S, Price RE, Wehrens XH, Cooper TA (2010) Heart-specific overexpression of CUGBP1 reproduces functional and molecular abnormalities of myotonic dystrophy type 1. Hum Mol Genet 19:1066–1075

    Google Scholar 

  • Kress C, Gautier-Courteille C, Osborne HB, Babinet C, Paillard L (2007) Inactivation of CUG-BP1/CELF1 causes growth, viability, and spermatogenesis defects in mice. Mol Cell Biol 27:1146–1157

    CAS  PubMed Central  PubMed  Google Scholar 

  • Krüger M, Linke WA (2011) The giant protein titin: a regulatory node that integrates myocyte signaling pathways. J Biol Chem 286:9905–9912

    PubMed Central  PubMed  Google Scholar 

  • Kuroyanagi H, Ohno G, Mitani S, Hagiwara M (2007) The Fox-1 family and SUP-12 coordinately regulate tissue-specific alternative splicing in vivo. Mol Cell Biol 27:8612–8621

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuroyanagi H (2009) Fox-1 family of RNA-binding proteins. Cell Mol Life Sci 66:3895–3907

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kuyumcu-Martinez NM, Wang GS, Cooper TA (2007) Increased steady-state levels of CUGBP1 in myotonic dystrophy 1 are due to PKC-mediated hyperphosphorylation. Mol Cell 28:68–78

    CAS  PubMed Central  PubMed  Google Scholar 

  • Labeit S, Kolmerer B (1995) Titins: giant proteins in charge of muscle ultrastructure and elasticity. Science 270:293–296

    CAS  PubMed  Google Scholar 

  • Ladd AN, Charlet N, Cooper TA (2001) The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing. Mol Cell Biol 21:1285–1296

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ladd AN, Taffet G, Hartley C, Kearney DL, Cooper TA (2005) Cardiac tissue-specific repression of CELF activity disrupts alternative splicing and causes cardiomyopathy. Mol Cell Biol 25:6267–6278

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lara-Pezzi E, Gómez-Salinero J, Gatto A, García-Pavía P (2013) The alternative heart: impact of alternative splicing in heart disease. J Cardiovasc Transl Res 6(6):945–955

    PubMed  Google Scholar 

  • Lee JE, Lee JY, Wilusz J, Tian B, Wilusz CJ (2010) Systematic analysis of cis-elements in unstable mRNAs demonstrates that CUGBP1 is a key regulator of mRNA decay in muscle cells. PLoS One 5:e11201. doi:10.1371/journal.pone.0011201

    PubMed Central  PubMed  Google Scholar 

  • Lemaire R, Prasad J, Kashima T, Gustafson J, Manley JL, Lafyatis R (2002) Stability of a PKCI-1-related mRNA is controlled by the splicing factor ASF/SF2: a novel function for SR proteins. Genes Dev 16:594–607

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li D, Bachinski LL, Roberts R (2001) Genomic organization and isoform-specific tissue expression of human NAPOR (CUGBP2) as a candidate gene for familial arrhythmogenic right ventricular dysplasia. Genomics 74:396–401

    CAS  PubMed  Google Scholar 

  • Li S, Guo W, Dewey CN, Greaser ML (2013) Rbm20 regulates titin alternative splicing as a splicing repressor. Nucleic Acids Res 41:2659–2672

    Google Scholar 

  • Li D, Morales A, Gonzalez-Quintana J, Norton N, Siegfried JD, Hofmeyer M, Hershberger RE (2010) Identification of novel mutations in RBM20 in patients with dilated cardiomyopathy. Clin Transl Sci 3:90–97

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lin S, Fu XD (2007) SR proteins and related factors in alternative splicing. Adv Exp Med Biol 623:107–122

    PubMed  Google Scholar 

  • Licatalosi DD, Darnell RB (2006) Splicing regulation in neurologic disease. Neuron 52:93–101

    CAS  PubMed  Google Scholar 

  • Lin X, Miller JW, Mankodi A, Kanadia RN, Yuan Y, Moxley RT, Swanson MS, Thornton CA (2006) Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy. Hum Mol Genet 15:2087–2097

    CAS  PubMed  Google Scholar 

  • Lichtner P, Attié-Bitach T, Schuffenhauer S, Henwood J, Bouvagnet P, Scambler PJ, Meitinger T, Vekemans M (2002) Expression and mutation analysis of BRUNOL3, a candidate gene for heart and thymus developmental defects associated with partial monosomy 10p. J Mol Med (Berl) 80:431–442

    CAS  Google Scholar 

  • Long JC, Caceres JF (2009) The SR protein family of splicing factors: master regulators of gene expression. Biochem J 417:15–27

    CAS  PubMed  Google Scholar 

  • Lu X, Timchenko NA, Timchenko LT (1999) Cardiac elav-type RNA-binding protein (ETR-3) binds to RNA CUG repeats expanded in myotonic dystrophy. Hum Mol Genet 8:53–60

    CAS  PubMed  Google Scholar 

  • Lukong KE, Chang KW, Khandjian EW, Richard S (2008) RNA-binding proteins in human genetic disease. Trends Genet 24:416–425

    CAS  PubMed  Google Scholar 

  • Machuca-Tzili LE, Buxton S, Thorpe A, Timson CM, Wigmore P, Luther PK, Brook JD (2011) Zebrafish deficient for Muscleblind-like 2 exhibit features of myotonic dystrophy. Dis Model Mech 4:381–392

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mahmoud AI, Kocabas F, Muralidhar SA, Kimura W, Koura AS, Thet S, Porrello ER, Sadek HA (2013) Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Nature 497:249–253

    CAS  PubMed  Google Scholar 

  • Makarenko I, Opitz CA, Leake MC, Neagoe C, Kulke M, Gwathmey JK, del Monte F, Hajjar RJ, Linke WA (2004) Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts. Circ Res 95:708–716

    CAS  PubMed  Google Scholar 

  • Makeyev EV, Zhang J, Carrasco MA, Maniatis T (2007) The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27:435–448

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mankodi A, Logigian E, Callahan L, McClain C, White R, Henderson D, Krym M, Thornton CA (2000) Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science 289:1769–1773

    CAS  PubMed  Google Scholar 

  • Mankodi A, Urbinati CR, Yuan QP, Moxley RT, Sansone V, Krym M, Henderson D, Schalling M, Swanson MS, Thornton CA (2001) Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2. Hum Mol Genet 10:2165–2170

    Google Scholar 

  • Mankodi A, Takahashi MP, Jiang H, Beck CL, Bowers WJ, Moxley RT, Cannon SC, Thornton CA (2002) Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell 10:35–44

    CAS  PubMed  Google Scholar 

  • Manley JL, Krainer AR (2010) A rational nomenclature for serine/arginine-rich protein splicing factors (SR proteins). Genes Dev 24:1073–1074

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maragh S, Miller RA, Bessling SL, McGaughey DM, Wessels MW, de Graaf B, Stone EA, Bertoli-Avella AM, Gearhart JD, Fisher S, McCallion AS (2011) Identification of RNA binding motif proteins essential for cardiovascular development. BMC Dev Biol 11:62. doi:10.1186/1471-213X-11-62

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marquis J, Paillard L, Audic Y, Cosson B, Danos O, Le Bec C, Osborne HB (2006) CUG-BP1/CELF1 requires UGU-rich sequences for high-affinity binding. Biochem J 400:291–301

    CAS  PubMed Central  PubMed  Google Scholar 

  • Martin CL, Duvall JA, Ilkin Y, Simon JS, Arreaza MG, Wilkes K, Alvarez-Retuerto A, Whichello A, Powell CM, Rao K et al (2007) Cytogenetic and molecular characterization of A2BP1/FOX1 as a candidate gene for autism. Am J Med Genet B Neuropsychiatr Genet 144B:869–876

    CAS  PubMed  Google Scholar 

  • Mason JW (2002) Viral latency: a link between myocarditis and dilated cardiomyopathy? J Mol Cell Cardiol 34:695–698

    CAS  PubMed  Google Scholar 

  • Masuda A, Andersen HS, Doktor TK, Okamoto T, Ito M, Andresen BS, Ohno K (2012) CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay. Sci Rep 2:209. doi:10.1038/srep00209

    PubMed Central  PubMed  Google Scholar 

  • McKee AE, Minet E, Stern C, Riahi S, Stiles CD, Silver PA (2005) A genome-wide in situ hybridization map of RNA-binding proteins reveals anatomically restricted expression in the developing mouse brain. BMC Dev Biol 5:14

    PubMed Central  PubMed  Google Scholar 

  • McKusick VA (1998) Mendelian inheritance in man. A catalog of human genes and genetic disorders. Johns Hopkins University Press, Baltimore, MD

    Google Scholar 

  • Merkin J, Russell C, Chen P, Burge CB (2012) Evolutionary dynamics of gene and isoform regulation in Mammalian tissues. Science 338:1593–1599

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton CA, Swanson MS (2000) Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J 19:4439–4448

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miller RA, Christoforou N, Pevsner J, McCallion AS, Gearhart JD (2008) Efficient array-based identification of novel cardiac genes through differentiation of mouse ESCs. PLoS One 3:e2176. doi:10.1371/journal.pone.0002176

    PubMed Central  PubMed  Google Scholar 

  • Mills JD, Janitz M (2012) Alternative splicing of mRNA in the molecular pathology of neurodegenerative diseases. Neurobiol Aging 33(1012):e11–e24

    PubMed  Google Scholar 

  • Miragoli M, Gaudesius G, Rohr S (2006) Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res 98:801–810

    CAS  PubMed  Google Scholar 

  • Misteli T, Cáceres JF, Clement JQ, Krainer AR, Wilkinson MF, Spector DL (1998) Serine phosphorylation of SR proteins is required for their recruitment to sites of transcription in vivo. J Cell Biol 143:297–307

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mitchell SA, Brown EC, Coldwell MJ, Jackson RJ, Willis AE (2001) Protein factor requirements of the Apaf-1 internal ribosome entry segment: roles of polypyrimidine tract binding protein and upstream of N-ras. Mol Cell Biol 21:3364–3374

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miyamoto S, Hidaka K, Jin D, Morisaki T (2009) RNA-binding proteins Rbm38 and Rbm24 regulate myogenic differentiation via p21-dependent and -independent regulatory pathways. Genes Cells 14:1241–1252

    CAS  PubMed  Google Scholar 

  • Moraes KC, Wilusz CJ, Wilusz J (2006) CUG-BP binds to RNA substrates and recruits PARN deadenylase. RNA 12:1084–1091

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mulligan GJ, Guo W, Wormsley S, Helfman DM (1992) Polypyrimidine tract binding protein interacts with sequences involved in alternative splicing of beta-tropomyosin pre-mRNA. J Biol Chem 267:25480–25487

    CAS  PubMed  Google Scholar 

  • Neagoe C, Kulke M, del Monte F, Gwathmey JK, de Tombe PP, Hajjar RJ, Linke WA (2002) Titin isoform switch in ischemic human heart disease. Circulation 106:1333–1341

    PubMed  Google Scholar 

  • Nelson TJ, Balza R Jr, Xiao Q, Misra RP (2005) SRF-dependent gene expression in isolated cardiomyocytes: regulation of genes involved in cardiac hypertrophy. J Mol Cell Cardiol 39:479–489

    CAS  PubMed  Google Scholar 

  • Obermann WM, Gautel M, Weber K, Fürst DO (1997) Molecular structure of the sarcomeric M band: mapping of titin and myosin binding domains in myomesin and the identification of a potential regulatory phosphorylation site in myomesin. EMBO J 16:211–220

    CAS  PubMed Central  PubMed  Google Scholar 

  • Oh SW, Pope RK, Smith KP, Crowley JL, Nebl T, Lawrence JB, Luna EJ (2003) Archvillin, a muscle-specific isoform of supervillin, is an early expressed component of the costameric membrane skeleton. J Cell Sci 116:2261–2275

    CAS  PubMed  Google Scholar 

  • Olson EN (2001) Development. The path to the heart and the road not taken. Science 291:2327–2328

    CAS  PubMed  Google Scholar 

  • Olson EN (2006) Gene regulatory networks in the evolution and development of the heart. Science 313:1922–1927

    CAS  PubMed  Google Scholar 

  • Osborne RJ, Lin X, Welle S, Sobczak K, O'Rourke JR, Swanson MS, Thornton CA (2009) Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy. Hum Mol Genet 18:1471–1481

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pascual M, Vicente M, Monferrer L, Artero R (2006) The Muscleblind family of proteins: an emerging class of regulators of developmentally programmed alternative splicing. Differentiation 74:65–80

    CAS  PubMed  Google Scholar 

  • Patton JG, Mayer SA, Tempst P, Nadal-Ginard B (1991) Characterization and molecular cloning of polypyrimidine tract-binding protein: a component of a complex necessary for pre-mRNA splicing. Genes Dev 5:1237–1251

    CAS  PubMed  Google Scholar 

  • Pelargonio G, Dello Russo A, Sanna T, De Martino G, Bellocci F (2002) Myotonic dystrophy and the heart. Heart 88:665–670

    CAS  PubMed Central  PubMed  Google Scholar 

  • Philips AV, Timchenko LT, Cooper TA (1998) Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. Science 280:737–741

    CAS  PubMed  Google Scholar 

  • Ponthier JL, Schluepen C, Chen W, Lersch RA, Gee SL, Hou VC, Lo AJ, Short SA, Chasis JA, Winkelmann JC, Conboy JG (2006) Fox-2 splicing factor binds to a conserved intron motif to promote inclusion of protein 4.1R alternative exon 16. J Biol Chem 281:12468–12474

    CAS  PubMed  Google Scholar 

  • Poon KL, Tan KT, Wei YY, Ng CP, Colman A, Korzh V, Xu XQ (2012) RNA-binding protein RBM24 is required for sarcomere assembly and heart contractility. Cardiovasc Res 94:418–427

    CAS  PubMed  Google Scholar 

  • Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA (2011a) Transient regenerative potential of the neonatal mouse heart. Science 331:1078–1080

    CAS  PubMed Central  PubMed  Google Scholar 

  • Porrello ER, Johnson BA, Aurora AB, Simpson E, Nam YJ, Matkovich SJ, Dorn GW 2nd, van Rooij E, Olson EN (2011b) MiR-15 family regulates postnatal mitotic arrest of cardiomyocytes. Circ Res 109:670–679

    CAS  PubMed Central  PubMed  Google Scholar 

  • Porrello ER (2013) microRNAs in cardiac development and regeneration. Clin Sci (Lond) 125:151–166

    Google Scholar 

  • Poulos MG, Batra R, Li M, Yuan Y, Zhang C, Darnell RB, Swanson MS (2013) Progressive impairment of muscle regeneration in muscleblind-like 3 isoform knockout mice. Hum Mol Genet 22(17):3547–3558

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rau F, Freyermuth F, Fugier C, Villemin JP, Fischer MC, Jost B, Dembele D, Gourdon G, Nicole A, Duboc D et al (2011) Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy. Nat Struct Mol Biol 18:840–845

    CAS  PubMed  Google Scholar 

  • Ranum LP, Cooper TA (2006) RNA-mediated neuromuscular disorders. Annu Rev Neurosci 29:259–277

    CAS  PubMed  Google Scholar 

  • Rattenbacher B, Beisang D, Wiesner DL, Jeschke JC, von Hohenberg M, St Louis-Vlasova IA, Bohjanen PR (2010) Analysis of CUGBP1 targets identifies GU-repeat sequences that mediate rapid mRNA decay. Mol Cell Biol 30:3970–3980

    CAS  PubMed Central  PubMed  Google Scholar 

  • Refaat MM, Lubitz SA, Makino S, Islam Z, Frangiskakis JM, Mehdi H, Gutmann R, Zhang ML, Bloom HL, MacRae CA et al (2012) Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm 9:390–396

    PubMed Central  PubMed  Google Scholar 

  • Riggi N, Cironi L, Suvà ML, Stamenkovic I (2007) Sarcomas: genetics, signalling, and cellular origins. Part 1: the fellowship of TET. J Pathol 213:4–20

    CAS  PubMed  Google Scholar 

  • Salisbury E, Sakai K, Schoser B, Huichalaf C, Schneider-Gold C, Nguyen H, Wang GL, Albrecht JH, Timchenko LT (2008) Ectopic expression of cyclin D3 corrects differentiation of DM1 myoblasts through activation of RNA CUG-binding protein, CUGBP1. Exp Cell Res 314: 2266–2278

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sanford JR, Gray NK, Beckmann K, Cáceres JF (2004) A novel role for shuttling SR proteins in mRNA translation. Genes Dev 18:755–768

    CAS  PubMed Central  PubMed  Google Scholar 

  • Savkur RS, Philips AV, Cooper TA (2001) Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 29:40–47

    CAS  PubMed  Google Scholar 

  • Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M (2007) MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 100:416–424

    CAS  PubMed  Google Scholar 

  • Schepens B, Tinton SA, Bruynooghe Y, Beyaert R, Cornelis S (2005) The polypyrimidine tract-binding protein stimulates HIF-1alpha IRES-mediated translation during hypoxia. Nucleic Acids Res 33:6884–6894

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schoser B, Timchenko L (2010) Myotonic dystrophies 1 and 2: complex diseases with complex mechanisms. Curr Genomics 11:77–90

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shin C, Manley JL (2002) The SR protein SRp38 represses splicing in M phase cells. Cell 111:407–417

    CAS  PubMed  Google Scholar 

  • Shin C, Feng Y, Manley JL (2004) Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock. Nature 427:553–558

    CAS  PubMed  Google Scholar 

  • Shu L, Yan W, Chen X (2006) RNPC1, an RNA-binding protein and a target of the p53 family, is required for maintaining the stability of the basal and stress-induced p21 transcript. Genes Dev 20:2961–2972

    CAS  PubMed Central  PubMed  Google Scholar 

  • Singh R, Valcárcel J, Green MR (1995) Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins. Science 268:1173–1176

    CAS  PubMed  Google Scholar 

  • Singh RK, Cooper TA (2012) Pre-mRNA splicing in disease and therapeutics. Trends Mol Med 18:472–482

    CAS  PubMed Central  PubMed  Google Scholar 

  • Song HW, Cauffman K, Chan AP, Zhou Y, King ML, Etkin LD, Kloc M (2007) Hermes RNA-binding protein targets RNAs-encoding proteins involved in meiotic maturation, early cleavage, and germline development. Differentiation 75:519–528

    CAS  PubMed  Google Scholar 

  • Song HK, Hong SE, Kim T, Kim do H (2012) Deep RNA sequencing reveals novel cardiac transcriptomic signatures for physiological and pathological hypertrophy. PLoS One 7:e35552. doi:10.1371/journal.pone.0035552

    CAS  PubMed Central  PubMed  Google Scholar 

  • Southby J, Gooding C, Smith CW (1999) Polypyrimidine tract binding protein functions as a repressor to regulate alternative splicing of alpha-actinin mutually exclusive exons. Mol Cell Biol 19:2699–2711

    CAS  PubMed Central  PubMed  Google Scholar 

  • Squillace RM, Chenault DM, Wang EH (2002) Inhibition of muscle differentiation by the novel muscleblind-related protein CHCR. Dev Biol 250:218–230

    CAS  PubMed  Google Scholar 

  • Srebrow A, Kornblihtt AR (2006) The connection between splicing and cancer. J Cell Sci 119:2635–2641

    CAS  PubMed  Google Scholar 

  • Srivastava D (2006) Making or breaking the heart: from lineage determination to morphogenesis. Cell 126:1037–1048

    CAS  PubMed  Google Scholar 

  • Suenaga K, Lee KY, Nakamori M, Tatsumi Y, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Du H, Ares M Jr et al (2012) Muscleblind-like 1 knockout mice reveal novel splicing defects in the myotonic dystrophy brain. PLoS One 7:e33218. doi:10.1371/journal.pone.0033218

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sawicka K, Bushell M, Spriggs KA, Willis AE (2008) Polypyrimidine-tract-binding protein: a multifunctional RNA-binding protein. Biochem Soc Trans 36:641–647

    CAS  PubMed  Google Scholar 

  • Takahashi N, Sasagawa N, Suzuki K, Ishiura S (2000) The CUG-binding protein binds specifically to UG dinucleotide repeats in a yeast three-hybrid system. Biochem Biophys Res Commun 277:518–523

    CAS  PubMed  Google Scholar 

  • Tang ZZ, Sharma S, Zheng S, Chawla G, Nikolic J, Black DL (2011) Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein. J Biol Chem 286:10007–10016

    CAS  PubMed Central  PubMed  Google Scholar 

  • Teplova M, Patel DJ (2008) Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1. Nat Struct Mol Biol 15:1343–1351

    CAS  PubMed  Google Scholar 

  • Terenzi F, Brimacombe KR, Penn MS, Ladd AN (2009) CELF-mediated alternative splicing is required for cardiac function during early, but not later, postnatal life. J Mol Cell Cardiol 46:395–404

    CAS  PubMed  Google Scholar 

  • Tian B, White RJ, Xia T, Welle S, Turner DH, Mathews MB, Thornton CA (2000) Expanded CUG repeat RNAs form hairpins that activate the double-stranded RNA-dependent protein kinase PKR. RNA 6:79–87

    CAS  PubMed Central  PubMed  Google Scholar 

  • Timchenko LT, Miller JW, Timchenko NA, DeVore DR, Datar KV, Lin L, Roberts R, Caskey CT, Swanson MS (1996) Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res 24:4407–4414

    CAS  PubMed Central  PubMed  Google Scholar 

  • Timchenko NA, Cai ZJ, Welm AL, Reddy S, Ashizawa T, Timchenko LT (2001a) RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1. J Biol Chem 276:7820–7826

    CAS  PubMed  Google Scholar 

  • Timchenko NA, Iakova P, Cai ZJ, Smith JR, Timchenko LT (2001b) Molecular basis for impaired muscle differentiation in myotonic dystrophy. Mol Cell Biol 21:6927–6938

    CAS  PubMed Central  PubMed  Google Scholar 

  • Timchenko LT, Salisbury E, Wang GL, Nguyen H, Albrecht JH, Hershey JW, Timchenko NA (2006) Age-specific CUGBP1-eIF2 complex increases translation of CCAAT/enhancer-binding protein beta in old liver. J Biol Chem 281:32806–32819

    CAS  PubMed  Google Scholar 

  • Tirziu D, Giordano FJ, Simons M (2010) Cell communications in the heart. Circulation 122:928–937

    PubMed Central  PubMed  Google Scholar 

  • Tran H, Gourrier N, Lemercier-Neuillet C, Dhaenens CM, Vautrin A, Fernandez-Gomez FJ, Arandel L, Carpentier C, Obriot H, Eddarkaoui S et al (2011) Analysis of exonic regions involved in nuclear localization, splicing activity, and dimerization of Muscleblind-like-1 isoforms. J Biol Chem 286:16435–16446

    CAS  PubMed Central  PubMed  Google Scholar 

  • Torchia EC, Boyd K, Rehg JE, Qu C, Baker SJ (2007) EWS/FLI-1 induces rapid onset of myeloid/erythroid leukemia in mice. Mol Cell Biol 27:7918–7934

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ule J, Jensen KB, Ruggiu M, Mele A, Ule A, Darnell RB (2003) CLIP identifies Nova-regulated RNA networks in the brain. Science 302:1212–1215

    CAS  PubMed  Google Scholar 

  • Underwood JG, Boutz PL, Dougherty JD, Stoilov P, Black DL (2005) Homologues of the Caenorhabditis elegans Fox-1 protein are neuronal splicing regulators in mammals. Mol Cell Biol 25:10005–10016

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vacchi-Suzzi C, Hahne F, Scheubel P, Marcellin M, Dubost V, Westphal M, Boeglen C, Büchmann-Møller S, Cheung MS, Cordier A et al (2013) Heart structure-specific transcriptomic atlas reveals conserved microRNA-mRNA interactions. PLoS One 8:e52442. doi:10.1371/journal.pone.0052442

    CAS  PubMed Central  PubMed  Google Scholar 

  • van Kouwenhove M, Kedde M, Agami R (2011) MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer 11:644–656

    Google Scholar 

  • van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, Richardson JA, Olson EN (2006) A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A 103:18255–18260

    PubMed Central  PubMed  Google Scholar 

  • van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN (2007) Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316:575–579

    PubMed  Google Scholar 

  • van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN (2008) Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A 105:13027–13032

    PubMed Central  PubMed  Google Scholar 

  • Vlasova IA, Tahoe NM, Fan D, Larsson O, Rattenbacher B, Sternjohn JR, Vasdewani J, Karypis G, Reilly CS, Bitterman PB, Bohjanen PR (2008) Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1. Mol Cell 29:263–270

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vercellotti GM (2001) Overview of infections and cardiovascular diseases. J Allergy Clin Immunol 108:S117–S120

    CAS  PubMed  Google Scholar 

  • Wang HY, Xu X, Ding JH, Bermingham JR Jr, Fu XD (2001) SC35 plays a role in T cell development and alternative splicing of CD45. Mol Cell 7:331–342

    CAS  PubMed  Google Scholar 

  • Wang GS, Kearney DL, De Biasi M, Taffet G, Cooper TA (2007) Elevation of RNA-binding protein CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy. J Clin Invest 117:2802–2811

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP, Burge CB (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456: 470–476

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang GS, Kuyumcu-Martinez MN, Sarma S, Mathur N, Wehrens XH, Cooper TA (2009) PKC inhibition ameliorates the cardiac phenotype in a mouse model of myotonic dystrophy type 1. J Clin Invest 119:3797–3806

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang ET, Cody NA, Jog S, Biancolella M, Wang TT, Treacy DJ, Luo S, Schroth GP, Housman DE, Reddy S et al (2012a) Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell 150:710–724

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang K, Deng G, Chen G, Liu M, Yi Y, Yang T, McMillan DR, Xiao X (2012b) Heat shock protein 70 inhibits hydrogen peroxide-induced nucleolar fragmentation via suppressing cleavage and down-regulation of nucleolin. Cell Stress Chaperones 17:121–130

    CAS  PubMed Central  PubMed  Google Scholar 

  • Warf MB, Berglund JA (2007) MBNL binds similar RNA structures in the CUG repeats of myotonic dystrophy and its pre-mRNA substrate cardiac troponin T. RNA 13:2238–2251

    CAS  PubMed Central  PubMed  Google Scholar 

  • Warren CM, Jordan MC, Roos KP, Krzesinski PR, Greaser ML (2003) Titin isoform expression in normal and hypertensive myocardium. Cardiovasc Res 59:86–94

    CAS  PubMed  Google Scholar 

  • Wendel HG, Silva RL, Malina A, Mills JR, Zhu H, Ueda T, Watanabe-Fukunaga R, Fukunaga R, Teruya-Feldstein J, Pelletier J, Lowe SW (2007) Dissecting eIF4E action in tumorigenesis. Genes Dev 21:3232–3237

    CAS  PubMed Central  PubMed  Google Scholar 

  • Williams L, Howell N, Pagano D, Andreka P, Vertesaljai M, Pecor T, Frenneaux M, Granzier H (2009) Titin isoform expression in aortic stenosis. Clin Sci (Lond) 117:237–242

    CAS  Google Scholar 

  • Wollerton MC, Gooding C, Robinson F, Brown EC, Jackson RJ, Smith CW (2001) Differential alternative splicing activity of isoforms of polypyrimidine tract binding protein (PTB). RNA 7:819–832

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu H, Sun S, Tu K, Gao Y, Xie B, Krainer AR, Zhu J (2010) A splicing-independent function of SF2/ASF in microRNA processing. Mol Cell 38:67–77

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xiao SH, Manley JL (1997) Phosphorylation of the ASF/SF2 RS domain affects both protein-protein and protein-RNA interactions and is necessary for splicing. Genes Dev 11: 334–344

    CAS  PubMed  Google Scholar 

  • Xu X, Yang D, Ding JH, Wang W, Chu PH, Dalton ND, Wang HY, Bermingham JR Jr, Ye Z, Liu F et al (2005) ASF/SF2-regulated CaMKIIdelta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle. Cell 120:59–72

    CAS  PubMed  Google Scholar 

  • Xu XQ, Soo SY, Sun W, Zweigerdt R (2009) Global expression profile of highly enriched cardiomyocytes derived from human embryonic stem cells. Stem Cells 27:2163–2174

    CAS  PubMed  Google Scholar 

  • Yang B, Lin H, Xiao J, Lu Y, Luo X, Li B, Zhang Y, Xu C, Bai Y, Wang H et al (2007) The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 13:486–491

    CAS  PubMed  Google Scholar 

  • Ye J, Llorian M, Cardona M, Rongvaux A, Moubarak RS, Comella JX, Bassel-Duby R, Flavell RA, Olson EN, Smith CW, Sanchis D (2013) A pathway involving HDAC5, cFLIP and caspases regulates expression of the splicing regulator polypyrimidine tract binding protein in the heart. J Cell Sci 126:1682–1691

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yeo GW, Xu X, Liang TY, Muotri AR, Carson CT, Coufal NG, Gage FH (2007) Alternative splicing events identified in human embryonic stem cells and neural progenitors. PLoS Comput Biol 3:1951–1967

    CAS  PubMed  Google Scholar 

  • Yeo GW, Coufal NG, Liang TY, Peng GE, Fu XD, Gage FH (2009) An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells. Nat Struct Mol Biol 16:130–137

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang X, Azhar G, Chai J, Sheridan P, Nagano K, Brown T, Yang J, Khrapko K, Borras AM, Lawitts J et al (2001) Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor. Am J Physiol Heart Circ Physiol 280:H1782–H1792

    CAS  PubMed  Google Scholar 

  • Zhang Q, Bethmann C, Worth NF, Davies JD, Wasner C, Feuer A, Ragnauth CD, Yi Q, Mellad JA, Warren DT et al (2007) Nesprin-1 and −2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet 16:2816–2833

    CAS  PubMed  Google Scholar 

  • Zhang C, Zhang Z, Castle J, Sun S, Johnson J, Krainer AR, Zhang MQ (2008) Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Genes Dev 22:2550–2563

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang J, Bahi N, Llovera M, Comella JX, Sanchis D (2009) Polypyrimidine tract binding proteins (PTB) regulate the expression of apoptotic genes and susceptibility to caspase-dependent apoptosis in differentiating cardiomyocytes. Cell Death Differ 16:1460–1468

    CAS  PubMed  Google Scholar 

  • Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129:303–317

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

J.G. is a Pew Latin American Fellow in the Biomedical Sciences supported by the Pew Charitable Trusts. T.A.C. is funded by the National Institutes of Health (R01HL045565, R01AR060733, and R01AR045653) and Muscular Dystrophy Association grants.

Author information

Authors and Affiliations

  1. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA

    Jimena Giudice & Thomas A. Cooper

  2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA

    Thomas A. Cooper

  3. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA

    Thomas A. Cooper

Authors
  1. Jimena Giudice
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas A. Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jimena Giudice or Thomas A. Cooper .

Editor information

Editors and Affiliations

  1. UCSD Moores Cancer Center, Institute for Genomic Medicine UCSD Stem Cell Program, La Jolla, California, USA

    Gene W. Yeo

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Giudice, J., Cooper, T.A. (2014). RNA-Binding Proteins in Heart Development. In: Yeo, G. (eds) Systems Biology of RNA Binding Proteins. Advances in Experimental Medicine and Biology, vol 825. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1221-6_11

Download citation

Publish with us

Policies and ethics

Search

Navigation