RT Journal Article SR Electronic T1 Global gene repression by Dicer-independent tRNA Fragments JF bioRxiv FD Cold Spring Harbor Laboratory SP 143974 DO 10.1101/143974 A1 Kuscu, Canan A1 Kumar, Pankaj A1 Kiran, Manjari A1 Su, Zhangli A1 Malik, Asrar A1 Dutta, Anindya YR 2017 UL http://biorxiv.org/content/early/2017/05/30/143974.abstract AB tRNA derived RNA fragments (tRFs) is an emerging group of small RNAs as abundant as miRNAs, and yet their roles are not well understood. Here, we focus on endogenous tRFs (18-22 bases) derived from 3’ end of human mature tRNAs (tRF-3) and their functions in gene repression. tRF-3 levels increase upon parental tRNA over-expression or tRNA induction by c-Myc oncogene activation. Elevated tRF-3 levels lead to repression of target genes with a sequence complementary to the tRF-3 in the 3’ UTR. The tRF-3-mediated repression is Dicer-independent, Argonaute-dependent and the targets are recognized by 5’ seed sequence rules similar to miRNAs. Furthermore, tRF-3s associate with GW proteins in P-bodies. RNA-seq identifies the endogenous target genes of tRF-3s that are specifically repressed upon tRF-3 induction. Overall, our analysis shows Dicer-independent tRF-3s, generated upon tRNA upregulation such as c-Myc overexpression, regulate gene expression globally through Argounate via seed sequence matches.