title: A novel class of small RNAs: tRNA-derived RNA fragments (tRFs).
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.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Yong Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Shibata
authors.forename: Ankit
authors.initials: A
authors.lastname: Malhotra
authors.forename: Anindya
authors.initials: A
authors.lastname: Dutta
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry* / Q000235:genetics*
chemical_list: C421605:ELAC2 protein, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012343:RNA, Transfer