Roquin targets mRNAs in a 3'-UTR-specific manner by different modes of regulation

Nat Commun. 2018 Sep 19;9(1):3810. doi: 10.1038/s41467-018-06184-3.


The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene expression and cell-fate decisions. Here, we show that Roquin not only interacts with stem-loop structures, but also with a linear sequence element present in about half of its targets. Comprehensive analysis of a minimal response element of the Nfkbid 3'-UTR shows that six stem-loop structures cooperate to exert robust and profound post-transcriptional regulation. Only binding of multiple Roquin proteins to several stem-loops exerts full repression, which redundantly involved deadenylation and decapping, but also translational inhibition. Globally, most Roquin targets are regulated by mRNA decay, whereas a small subset, including the Nfat5 mRNA, with more binding sites in their 3'-UTRs, are also subject to translational inhibition. These findings provide insights into how the robustness and magnitude of Roquin-mediated regulation is encoded in complex cis-elements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Amino Acid Motifs
  • Animals
  • Base Sequence
  • Binding Sites
  • Cross-Linking Reagents / chemistry
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Mice
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Biosynthesis
  • RNA Stability / genetics
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Response Elements / genetics
  • Ribonucleosides / metabolism
  • Transcriptome / genetics
  • Ubiquitin-Protein Ligases / metabolism*


  • 3' Untranslated Regions
  • Cross-Linking Reagents
  • RNA, Messenger
  • Ribonucleosides
  • Rc3h1 protein, mouse
  • Ubiquitin-Protein Ligases