Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Review

Microprocessor of microRNAs: regulation and potential for therapeutic intervention

Authors: Kevin J Beezhold, Vince Castranova, Fei Chen

Published in: Molecular Cancer | Issue 1/2010

Login to get access

Abstract

MicroRNAs (miRNAs) are a class of small, noncoding RNAs critically involved in a wide spectrum of normal and pathological processes of cells or tissues by fine-tuning the signals important for stem cell development, cell differentiation, cell cycle regulation, apoptosis, and transformation. Considerable progress has been made in the past few years in understanding the transcription, biogenesis and functional regulation of miRNAs. Numerous studies have implicated altered expression of miRNAs in human cancers, suggesting that aberrant expression of miRNAs is one of the hallmarks for carcinogenesis. In this review, we briefly discuss most recent discoveries on the regulation of miRNAs at the level of microprocessor-mediated biogenesis of miRNAs.
Appendix
Available only for authorised users
Literature
1.
2.
Lee Y, Jeon K, Lee JT, Kim S, Kim VN: MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002, 21: 4663-4670. 10.1093/emboj/cdf476PubMedCentralCrossRefPubMed
3.
Hutvagner G, McLachlan J, Pasquinelli AE: A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001, 293: 834-838. 10.1126/science.1062961CrossRefPubMed
4.
Lee Y, Ahn C, Han J: The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003, 425: 415-419. 10.1038/nature01957CrossRefPubMed
5.
Yi R, Qin Y, Macara IG, Cullen BR: Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003, 17: 3011-3016. 10.1101/gad.1158803PubMedCentralCrossRefPubMed
6.
Bohnsack MT, Czaplinski K, Gorlich D: Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA. 2004, 10: 185-191. 10.1261/rna.5167604PubMedCentralCrossRefPubMed
7.
Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U: Nuclear export of microRNA precursors. Science. 2004, 303: 95-98. 10.1126/science.1090599CrossRefPubMed
8.
Zeng Y, Cullen BR: Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res. 2004, 32: 4776-4785. 10.1093/nar/gkh824PubMedCentralCrossRefPubMed
9.
Bernstein E, Caudy AA, Hammond SM, Hannon GJ: Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001, 409: 363-366. 10.1038/35053110CrossRefPubMed
10.
Ketting RF, Fischer SE, Bernstein E: Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. Genes Dev. 2001, 15: 2654-2659. 10.1101/gad.927801PubMedCentralCrossRefPubMed
11.
Knight SW, Bass BL: A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science. 2001, 293: 2269-2271. 10.1126/science.1062039PubMedCentralCrossRefPubMed
12.
Zhang H, Kolb FA, Brondani V, Billy E, Filipowicz W: Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J. 2002, 21: 5875-5885. 10.1093/emboj/cdf582PubMedCentralCrossRefPubMed
13.
MacRae IJ, Zhou K, Doudna JA: Structural determinants of RNA recognition and cleavage by Dicer. Nat Struct Mol Biol. 2007, 14: 934-940. 10.1038/nsmb1293CrossRefPubMed
14.
Khvorova A, Reynolds A, Jayasena SD: Functional siRNAs and miRNAs exhibit strand bias. Cell. 2003, 115: 209-216. 10.1016/S0092-8674(03)00801-8CrossRefPubMed
15.
Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R: Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 2005, 123: 631-640. 10.1016/j.cell.2005.10.022CrossRefPubMed
16.
Pusch O, Boden D, Silbermann R: Nucleotide sequence homology requirements of HIV-1-specific short hairpin RNA. Nucleic Acids Res. 2003, 31: 6444-6449. 10.1093/nar/gkg876PubMedCentralCrossRefPubMed
17.
18.
Lal A, Navarro F, Maher CA: miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements. Mol Cell. 2009, 35: 610-625. 10.1016/j.molcel.2009.08.020PubMedCentralCrossRefPubMed
19.
Cannell IG, Kong YW, Bushell M: How do microRNAs regulate gene expression?. Biochem Soc Trans. 2008, 36: 1224-1231. 10.1042/BST0361224CrossRefPubMed
20.
Zamore PD, Tuschl T, Sharp PA, Bartel DP: RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell. 2000, 101: 25-33. 10.1016/S0092-8674(00)80620-0CrossRefPubMed
21.
Moss EG, Lee RC, Ambros V: The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell. 1997, 88: 637-646. 10.1016/S0092-8674(00)81906-6CrossRefPubMed
22.
Vella MC, Reinert K, Slack FJ: Architecture of a validated microRNA::target interaction. Chem Biol. 2004, 11: 1619-1623. 10.1016/j.chembiol.2004.09.010CrossRefPubMed
23.
Wu L, Belasco JG: Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs. Mol Cell. 2008, 29: 1-7. 10.1016/j.molcel.2007.12.010CrossRefPubMed
24.
Pillai RS, Bhattacharyya SN, Artus CG: Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science. 2005, 309: 1573-1576. 10.1126/science.1115079CrossRefPubMed
25.
Kiriakidou M, Tan GS, Lamprinaki S: An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell. 2007, 129: 1141-1151. 10.1016/j.cell.2007.05.016CrossRefPubMed
26.
Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R: MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005, 7: 719-723. 10.1038/ncb1274PubMedCentralCrossRefPubMed
27.
28.
Rehwinkel J, Behm-Ansmant I, Gatfield D, Izaurralde E: A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. Rna. 2005, 11: 1640-1647. 10.1261/rna.2191905PubMedCentralCrossRefPubMed
29.
Jackson RJ, Standart N: How do microRNAs regulate gene expression?. Sci STKE. 2007, 2007: re1- 10.1126/stke.3672007re1CrossRefPubMed
30.
Seitz H, Zamore PD: Rethinking the microprocessor. Cell. 2006, 125: 827-829. 10.1016/j.cell.2006.05.018CrossRefPubMed
31.
Morlando M, Ballarino M, Gromak N: Primary microRNA transcripts are processed co-transcriptionally. Nat Struct Mol Biol. 2008, 15: 902-909. 10.1038/nsmb.1475CrossRefPubMed
32.
Gregory RI, Yan KP, Amuthan G: The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004, 432: 235-240. 10.1038/nature03120CrossRefPubMed
33.
34.
Zeng Y, Yi R, Cullen BR: Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 2005, 24: 138-148. 10.1038/sj.emboj.7600491PubMedCentralCrossRefPubMed
35.
Chen CZ, Li L, Lodish HF, Bartel DP: MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004, 303: 83-86. 10.1126/science.1091903CrossRefPubMed
36.
Han J, Lee Y, Yeom KH: Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006, 125: 887-901. 10.1016/j.cell.2006.03.043CrossRefPubMed
37.
Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N: Nucleolar localization of DGCR8 and identification of eleven DGCR8-associated proteins. Exp Cell Res. 2007, 313: 4196-4207. 10.1016/j.yexcr.2007.07.020CrossRefPubMed
38.
Fuller-Pace FV: DExD/H box RNA helicases: multifunctional proteins with important roles in transcriptional regulation. Nucleic Acids Res. 2006, 34: 4206-4215. 10.1093/nar/gkl460PubMedCentralCrossRefPubMed
39.
Fukuda T, Yamagata K, Fujiyama S: DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. Nat Cell Biol. 2007, 9: 604-611. 10.1038/ncb1577CrossRefPubMed
40.
41.
Warner DR, Bhattacherjee V, Yin X: Functional interaction between Smad, CREB binding protein, and p68 RNA helicase. Biochem Biophys Res Commun. 2004, 324: 70-76. 10.1016/j.bbrc.2004.09.017CrossRefPubMed
42.
43.
Selcuklu SD, Donoghue MT, Spillane C: miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans. 2009, 37: 918-925. 10.1042/BST0370918CrossRefPubMed
44.
Yamanaka Y, Tagawa H, Takahashi N: Aberrant overexpression of microRNAs activate AKT signaling via downregulation of tumor suppressors in NK-cell lymphoma/leukemia. Blood. 2009, 114 (15): 3265-75. 10.1182/blood-2009-06-222794CrossRefPubMed
45.
Asangani IA, Rasheed SA, Nikolova DA: MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 2008, 27: 2128-2136. 10.1038/sj.onc.1210856CrossRefPubMed
46.
Garzon R, Volinia S, Liu CG: MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood. 2008, 111: 3183-3189. 10.1182/blood-2007-07-098749PubMedCentralCrossRefPubMed
47.
Chen R, Alvero AB, Silasi DA: Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells. Oncogene. 2008, 27: 4712-4723. 10.1038/onc.2008.112PubMedCentralCrossRefPubMed
48.
Kong W, Yang H, He L: MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targeting RhoA. Mol Cell Biol. 2008, 28: 6773-6784. 10.1128/MCB.00941-08PubMedCentralCrossRefPubMed
49.
Yang H, Kong W, He L: MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008, 68: 425-433. 10.1158/0008-5472.CAN-07-2488CrossRefPubMed
50.
Suzuki HI, Yamagata K, Sugimoto K: Modulation of microRNA processing by p53. Nature. 2009, 460: 529-533. 10.1038/nature08199CrossRefPubMed
51.
Bates GJ, Nicol SM, Wilson BJ: The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. EMBO J. 2005, 24: 543-553. 10.1038/sj.emboj.7600550PubMedCentralCrossRefPubMed
52.
Raver-Shapira N, Marciano E, Meiri E: Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007, 26: 731-743. 10.1016/j.molcel.2007.05.017CrossRefPubMed
53.
Zenz T, Mohr J, Eldering E: miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood. 2009, 113: 3801-3808. 10.1182/blood-2008-08-172254CrossRefPubMed
54.
Fujita Y, Kojima K, Hamada N: Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun. 2008, 377: 114-119. 10.1016/j.bbrc.2008.09.086CrossRefPubMed
55.
Tazawa H, Tsuchiya N, Izumiya M, Nakagama H: Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci USA. 2007, 104: 15472-15477. 10.1073/pnas.0707351104PubMedCentralCrossRefPubMed
56.
Li Y, Guessous F, Zhang Y: MicroRNA-34a Inhibits Glioblastoma Growth by Targeting Multiple Oncogenes. Cancer Res. 2009, 69 (19): 7569-76. 10.1158/0008-5472.CAN-09-0529PubMedCentralCrossRefPubMed
57.
Lerner M, Harada M, Loven J: DLEU2, frequently deleted in malignancy, functions as a critical host gene of the cell cycle inhibitory microRNAs miR-15a and miR-16-1. Exp Cell Res. 2009, 315 (17): 2941-52. 10.1016/j.yexcr.2009.07.001CrossRefPubMed
58.
Cimmino A, Calin GA, Fabbri M: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005, 102: 13944-13949. 10.1073/pnas.0506654102PubMedCentralCrossRefPubMed
59.
Bonci D, Coppola V, Musumeci M: The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008, 14: 1271-1277. 10.1038/nm.1880CrossRefPubMed
60.
Slaby O, Svoboda M, Fabian P: Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 2007, 72: 397-402. 10.1159/000113489CrossRefPubMed
61.
Motoyama K, Inoue H, Takatsuno Y: Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 2009, 34: 1069-1075.PubMed
62.
63.
Chen X, Guo X, Zhang H: Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene. 2009, 28: 1385-1392. 10.1038/onc.2008.474CrossRefPubMed
64.
Wang S, Bian C, Yang Z: miR-145 inhibits breast cancer cell growth through RTKN. Int J Oncol. 2009, 34: 1461-1466.PubMed
65.
Wilson MD, Wang D, Wagner R: ARS2 is a conserved eukaryotic gene essential for early mammalian development. Mol Cell Biol. 2008, 28: 1503-1514. 10.1128/MCB.01565-07PubMedCentralCrossRefPubMed
66.
Gruber JJ, Zatechka DS, Sabin LR: Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell. 2009, 138: 328-339. 10.1016/j.cell.2009.04.046PubMedCentralCrossRefPubMed
67.
Dong Z, Han MH, Fedoroff N: The RNA-binding proteins HYL1 and SE promote accurate in vitro processing of pri-miRNA by DCL1. Proc Natl Acad Sci USA. 2008, 105: 9970-9975. 10.1073/pnas.0803356105PubMedCentralCrossRefPubMed
68.
Sabin LR, Zhou R, Gruber JJ: Ars2 regulates both miRNA- and siRNA-dependent silencing and suppresses RNA virus infection in Drosophila. Cell. 2009, 138: 340-351. 10.1016/j.cell.2009.04.045PubMedCentralCrossRefPubMed
69.
Hwang HW, Wentzel EA, Mendell JT: Cell-cell contact globally activates microRNA biogenesis. Proc Natl Acad Sci USA. 2009, 106: 7016-7021. 10.1073/pnas.0811523106PubMedCentralCrossRefPubMed
70.
Meerson A, Milyavsky M, Rotter V: p53 mediates density-dependent growth arrest. FEBS Lett. 2004, 559: 152-158. 10.1016/S0014-5793(04)00027-4CrossRefPubMed
71.
Yamagata KF, Ito S, Ueda S, Murata T, Naitou T, Takeyama M, Minami K, O'Malley Y, BW Kato S: Maturation of MicroRNA Is Hormonally Regulated by a Nuclear Receptor. Mol Cell. 2009, 36: 340-347. 10.1016/j.molcel.2009.08.017CrossRefPubMed
72.
Wong CF, Tellam RL: MicroRNA-26a targets the histone methyltransferase Enhancer of Zeste homolog 2 during myogenesis. J Biol Chem. 2008, 283: 9836-9843. 10.1074/jbc.M709614200CrossRefPubMed
Metadata
Title
Microprocessor of microRNAs: regulation and potential for therapeutic intervention
Authors
Kevin J Beezhold
Vince Castranova
Fei Chen
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-134

Other articles of this Issue 1/2010

Molecular Cancer 1/2010 Go to the issue

Research

Effects of nilotinib on regulatory T cells: the dose matters

Research

Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols

Research

Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells

Research

Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors

Research

Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

Research

Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits