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

By Yong Sun Lee, Y. Shibata, Ankit Malhotra, Anindya Dutta. Genes & Development, 2009

1,097 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bd9f18e46ac4b12f980f0eec5a7984dbce194e4e

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Citations in the corpus

The human mitochondrial transcriptome (2011, positive): “It was recently shown that nuclear tRNAs are processed by both Dicer-and RNaseZ-dependent pathways into a range of small RNA species that are subsequently incorporated into RNA-silencing pathways (Haussecker et al., 2010; Lee et al., 2009).”
Human tRNA-derived small RNAs in the global regulation of RNA silencing. (2010, background): “As such a modification pattern would be predicted to interfere with passenger strand cleavage by Ago2 (Leuschner et al. 2006), our results suggest that the relative ability of Ago2 for loading fully duplexed small RNAs is independent of its Slicer activity.”
An overview of microRNAs (2015, background): “Another class is derived from outside the mature tRNA and is generated by the tRNA splicing reaction[89, 90].”
Angiogenin-induced tRNA fragments inhibit translation initiation (2011, background): “, 2009) and the tRNA 30 end processing enzyme RNase Z (Haussecker et al., 2010; Lee et al., 2009).”
Bacterial small RNA regulators: versatile roles and rapidly evolving variations. (2011, result): “This prediction is supported by recent studies in eukaryotic cells (Cole et al. 2009; Lee et al. 2009; Thompson and Parker 2009); investigations of functions for tRNA fragments in bacteria have not yet been reported.”
Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions (2012, background): “We next explored whether these reads could represent tRNA fragments (tRFs), which have recently gained interest due to their suspected regulatory nature (45).”
Human box C/D snoRNAs with miRNA like functions: expanding the range of regulatory RNAs (2010, background): “New members of this family are tiRNAs, which apparently are involved in promoter transcriptional gene regulation via TSS interaction (14) or, very recently, tRNA transcript-derived RNA fragments, or tRFs, which are not yet functionally characterized, but aberrantly induce proliferative defects when ”