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A novel class of small RNAs: tRNA-derived RNA fragments (tRFs).
Genes Dev. 2009 Nov 15; 23(22):2639-49.GD

Abstract

New types of small RNAs distinct from microRNAs (miRNAs) are progressively being discovered in various organisms. In order to discover such novel small RNAs, a library of 17- to 26-base-long RNAs was created from prostate cancer cell lines and sequenced by ultra-high-throughput sequencing. A significant number of the sequences are derived from precise processing at the 5' or 3' end of mature or precursor tRNAs to form three series of tRFs (tRNA-derived RNA fragments): the tRF-5, tRF-3, and tRF-1 series. These sequences constitute a class of short RNAs that are second most abundant to miRNAs. Northern hybridization, quantitative RT-PCR, and splinted ligation assays independently measured the levels of at least 17 tRFs. To demonstrate the biological importance of tRFs, we further investigated tRF-1001, derived from the 3' end of a Ser-TGA tRNA precursor transcript that is not retained in the mature tRNA. tRF-1001 is expressed highly in a wide range of cancer cell lines but much less in tissues, and its expression in cell lines was tightly correlated with cell proliferation. siRNA-mediated knockdown of tRF-1001 impaired cell proliferation with the specific accumulation of cells in G2, phenotypes that were reversed specifically by cointroducing a synthetic 2'-O-methyl tRF-1001 oligoribonucleotide resistant to the siRNA. tRF-1001 is generated in the cytoplasm by tRNA 3'-endonuclease ELAC2, a prostate cancer susceptibility gene. Our data suggest that tRFs are not random by-products of tRNA degradation or biogenesis, but an abundant and novel class of short RNAs with precise sequence structure that have specific expression patterns and specific biological roles.

Authors+Show Affiliations

Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

19933153

Citation

Lee, Yong Sun, et al. "A Novel Class of Small RNAs: tRNA-derived RNA Fragments (tRFs)." Genes & Development, vol. 23, no. 22, 2009, pp. 2639-49.
Lee YS, Shibata Y, Malhotra A, et al. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009;23(22):2639-49.
Lee, Y. S., Shibata, Y., Malhotra, A., & Dutta, A. (2009). A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes & Development, 23(22), 2639-49. https://doi.org/10.1101/gad.1837609
Lee YS, et al. A Novel Class of Small RNAs: tRNA-derived RNA Fragments (tRFs). Genes Dev. 2009 Nov 15;23(22):2639-49. PubMed PMID: 19933153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). AU - Lee,Yong Sun, AU - Shibata,Yoshiyuki, AU - Malhotra,Ankit, AU - Dutta,Anindya, PY - 2009/11/26/entrez PY - 2009/11/26/pubmed PY - 2009/12/16/medline SP - 2639 EP - 49 JF - Genes & development JO - Genes Dev. VL - 23 IS - 22 N2 - New types of small RNAs distinct from microRNAs (miRNAs) are progressively being discovered in various organisms. In order to discover such novel small RNAs, a library of 17- to 26-base-long RNAs was created from prostate cancer cell lines and sequenced by ultra-high-throughput sequencing. A significant number of the sequences are derived from precise processing at the 5' or 3' end of mature or precursor tRNAs to form three series of tRFs (tRNA-derived RNA fragments): the tRF-5, tRF-3, and tRF-1 series. These sequences constitute a class of short RNAs that are second most abundant to miRNAs. Northern hybridization, quantitative RT-PCR, and splinted ligation assays independently measured the levels of at least 17 tRFs. To demonstrate the biological importance of tRFs, we further investigated tRF-1001, derived from the 3' end of a Ser-TGA tRNA precursor transcript that is not retained in the mature tRNA. tRF-1001 is expressed highly in a wide range of cancer cell lines but much less in tissues, and its expression in cell lines was tightly correlated with cell proliferation. siRNA-mediated knockdown of tRF-1001 impaired cell proliferation with the specific accumulation of cells in G2, phenotypes that were reversed specifically by cointroducing a synthetic 2'-O-methyl tRF-1001 oligoribonucleotide resistant to the siRNA. tRF-1001 is generated in the cytoplasm by tRNA 3'-endonuclease ELAC2, a prostate cancer susceptibility gene. Our data suggest that tRFs are not random by-products of tRNA degradation or biogenesis, but an abundant and novel class of short RNAs with precise sequence structure that have specific expression patterns and specific biological roles. SN - 1549-5477 UR - https://www.unboundmedicine.com/medline/citation/19933153/A_novel_class_of_small_RNAs:_tRNA_derived_RNA_fragments__tRFs__ L2 - http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=19933153 DB - PRIME DP - Unbound Medicine ER -