The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA function

Nucleic Acids Res. 2013 Jan 7;41(1):518-32. doi: 10.1093/nar/gks1032. Epub 2012 Nov 3.

Abstract

TRIM-NHL proteins are conserved regulators of development and differentiation but their molecular function has remained largely elusive. Here, we report an as yet unrecognized activity for the mammalian TRIM-NHL protein TRIM71 as a repressor of mRNAs. We show that TRIM71 is associated with mRNAs and that it promotes translational repression and mRNA decay. We have identified Rbl1 and Rbl2, two transcription factors whose down-regulation is important for stem cell function, as TRIM71 targets in mouse embryonic stem cells. Furthermore, one of the defining features of TRIM-NHL proteins, the NHL domain, is necessary and sufficient to target TRIM71 to RNA, while the RING domain that confers ubiquitin ligase activity is dispensable for repression. Our results reveal strong similarities between TRIM71 and Drosophila BRAT, the best-studied TRIM-NHL protein and a well-documented translational repressor, suggesting that BRAT and TRIM71 are part of a family of mRNA repressors regulating proliferation and differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryonic Stem Cells / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / metabolism
  • Point Mutation
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • RNA Stability
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / antagonists & inhibitors
  • Ribonucleoproteins / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • LIN-41 protein, mouse
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • Ribonucleoproteins
  • Transcription Factors
  • messenger ribonucleoprotein