Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets

BMC Biology

Research Article

Pankaj Kumar¹  Jordan Anaya¹  Anindya Dutta²  Suresh B Mudunuri³ 

[1] Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, 22901, Charlottesville, VA, USA;Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, 22901, Charlottesville, VA, USA;PO Box 800733, 1340 Jefferson Park, Ave Jordan Hall Room 1232, Charlottesville, VA, USA;Department of Computer Science and Engineering, Grandhi Varalakshmi Venkatarao Institute of Technology (GVIT), 534207, BhimavaramAndhra Pradesh, India;

关键词: Small RNA;    Non-coding RNA;    Regulatory RNA;    tRF;    tRNA;   

DOI  :  10.1186/s12915-014-0078-0

 received in 2014-08-21, accepted in 2014-09-18,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundtRFs, 14 to 32 nt long single-stranded RNA derived from mature or precursor tRNAs, are a recently discovered class of small RNA that have been found to be present in diverse organisms at read counts comparable to miRNAs. Currently, there is a debate about their biogenesis and function.ResultsThis is the first meta-analysis of tRFs. Analysis of more than 50 short RNA libraries has revealed that tRFs are precisely generated fragments present in all domains of life (bacteria to humans), and are not produced by the miRNA biogenesis pathway. Human PAR-CLIP data shows a striking preference for tRF-5s and tRF-3s to associate with AGO1, 3 and 4 rather than AGO2, and analysis of positional T to C mutational frequency indicates these tRFs associate with Argonautes in a manner similar to miRNAs. The reverse complements of canonical seed positions in these sequences match cross-link centered regions, suggesting these tRF-5s and tRF-3s interact with RNAs in the cell. Consistent with these results, human AGO1 CLASH data contains thousands of tRF-5 and tRF-3 reads chimeric with mRNAs.ConclusionstRFs are an abundant class of small RNA present in all domains of life whose biogenesis is distinct from miRNAs. In human HEK293 cells tRFs associate with Argonautes 1, 3 and 4 and not Argonaute 2 which is the main effector protein of miRNA function, but otherwise have very similar properties to miRNAs, indicating tRFs may play a major role in RNA silencing.

【 授权许可】

Unknown   
© Kumar et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.