Metazoan tRNA introns generate stable circular RNAs in vivo
- Zhipeng Lu1,
- Grigory S. Filonov2,
- John J. Noto3,
- Casey A. Schmidt3,
- Talia L. Hatkevich3,
- Ying Wen4,
- Samie R. Jaffrey2 and
- A. Gregory Matera1,3,4,5,6
- 1Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
- 2Department of Pharmacology, Weill Cornell Medical College, New York, New York 10065, USA
- 3Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
- 4Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA
- 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
- 6Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA
- Corresponding author: matera{at}unc.edu
Abstract
We report the discovery of a class of abundant circular noncoding RNAs that are produced during metazoan tRNA splicing. These transcripts, termed tRNA intronic circular (tric)RNAs, are conserved features of animal transcriptomes. Biogenesis of tricRNAs requires anciently conserved tRNA sequence motifs and processing enzymes, and their expression is regulated in an age-dependent and tissue-specific manner. Furthermore, we exploited this biogenesis pathway to develop an in vivo expression system for generating “designer” circular RNAs in human cells. Reporter constructs expressing RNA aptamers such as Spinach and Broccoli can be used to follow the transcription and subcellular localization of tricRNAs in living cells. Owing to the superior stability of circular vs. linear RNA isoforms, this expression system has a wide range of potential applications, from basic research to pharmaceutical science.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.052944.115.
- Received June 22, 2015.
- Accepted July 6, 2015.
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