A novel class of small RNAs: tRNA-derived RNA fragments (tRFs)

Yong Sun Lee, Yoshiyuki Shibata, Ankit Malhotra, Anindya Dutta

Research output: Contribution to journalArticle

493 Scopus citations

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 59 or 39 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 39 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 29-O-methyl tRF-1001 oligoribonucleotide resistant to the siRNA. tRF-1001 is generated in the cytoplasm by tRNA 39-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.

Original languageEnglish (US)
Pages (from-to)2639-2649
Number of pages11
JournalGenes and Development
Volume23
Issue number22
DOIs
StatePublished - Nov 15 2009

Keywords

  • Cancer cell proliferation
  • Deep sequencing
  • Small RNA
  • tRNA

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Lee, Y. S., Shibata, Y., Malhotra, A., & Dutta, A. (2009). A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes and Development, 23(22), 2639-2649. https://doi.org/10.1101/gad.1837609