LIN41 Post-transcriptionally Silences mRNAs by Two Distinct and Position-Dependent Mechanisms

Mol Cell. 2017 Feb 2;65(3):476-489.e4. doi: 10.1016/j.molcel.2016.12.010. Epub 2017 Jan 19.


The RNA-binding protein (RBP) LIN41, also known as LIN-41 or TRIM71, is a key regulator of animal development, but its physiological targets and molecular mechanism of action are largely elusive. Here we find that this RBP has two distinct mRNA-silencing activities. Using genome-wide ribosome profiling, RNA immunoprecipitation, and in vitro-binding experiments, we identify four mRNAs, each encoding a transcription factor or cofactor, as direct physiological targets of C. elegans LIN41. LIN41 silences three of these targets through their 3' UTRs, but it achieves isoform-specific silencing of one target, lin-29A, through its unique 5' UTR. Whereas the 3' UTR targets mab-10, mab-3, and dmd-3 undergo transcript degradation, lin-29A experiences translational repression. Through binding site transplantation experiments, we demonstrate that it is the location of the LIN41-binding site that specifies the silencing mechanism. Such position-dependent dual activity may, when studied more systematically, emerge as a feature shared by other RBPs.

Keywords: 3′ UTR; 5′ UTR; EGR; RNA-binding protein; heterochronic; mRNA degradation; positional effect; ribosome profiling; stem cell; translational repression.

MeSH terms

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • Animals
  • Binding Sites
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / metabolism*
  • RNA Interference
  • RNA Stability
  • RNA, Helminth / chemistry
  • RNA, Helminth / metabolism
  • RNA, Messenger / chemistry*
  • RNA, Messenger / metabolism*
  • Transcription Factors / metabolism*


  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • LIN-41 protein, C elegans
  • RNA, Helminth
  • RNA, Messenger
  • Transcription Factors