tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner

RNA. 2018 Aug;24(8):1093-1105. doi: 10.1261/rna.066126.118. Epub 2018 May 29.

Abstract

tRNA related RNA fragments (tRFs), also known as tRNA-derived RNAs (tdRNAs), are abundant small RNAs reported to be associated with Argonaute proteins, yet their function is unclear. We show that endogenous 18 nucleotide tRFs derived from the 3' ends of tRNAs (tRF-3) post-transcriptionally repress genes in HEK293T cells in culture. tRF-3 levels increase upon parental tRNA overexpression. This represses 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 sequence complementarity. Furthermore, tRF-3:target mRNA pairs in the RNA induced silencing complex associate with GW182 proteins, known to repress translation and promote the degradation of target mRNAs. RNA-seq demonstrates that endogenous target genes are specifically decreased upon tRF-3 induction. Therefore, Dicer-independent tRF-3s, generated upon tRNA overexpression, repress genes post-transcriptionally through an Argonaute-GW182 containing RISC via sequence matches with target mRNAs.

Keywords: post-transcriptional gene regulation; small noncoding RNA; tRF; tRNA fragments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Argonaute Proteins / genetics*
  • Autoantigens / metabolism*
  • Cell Line
  • DEAD-box RNA Helicases / genetics*
  • Eukaryotic Initiation Factors / genetics*
  • Gene Expression Regulation / genetics*
  • HEK293 Cells
  • Humans
  • Protein Processing, Post-Translational / genetics
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Transfer / genetics*
  • RNA-Binding Proteins / metabolism*
  • Ribonuclease III / genetics*

Substances

  • AGO1 protein, human
  • AGO2 protein, human
  • AGO3 protein, human
  • Argonaute Proteins
  • Autoantigens
  • Eukaryotic Initiation Factors
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • TNRC6A protein, human
  • RNA, Transfer
  • DICER1 protein, human
  • DROSHA protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases