Roquin Promotes Constitutive mRNA Decay via a Conserved Class of Stem-Loop Recognition Motifs

Cell. 2013 May 9;153(4):869-81. doi: 10.1016/j.cell.2013.04.016.

Abstract

Tumor necrosis factor-α (TNF-α) is the most potent proinflammatory cytokine in mammals. The degradation of TNF-α mRNA is critical for restricting TNF-α synthesis and involves a constitutive decay element (CDE) in the 3' UTR of the mRNA. Here, we demonstrate that the CDE folds into an RNA stem-loop motif that is specifically recognized by Roquin and Roquin2. Binding of Roquin initiates degradation of TNF-α mRNA and limits TNF-α production in macrophages. Roquin proteins promote mRNA degradation by recruiting the Ccr4-Caf1-Not deadenylase complex. CDE sequences are highly conserved and are found in more than 50 vertebrate mRNAs, many of which encode regulators of development and inflammation. In macrophages, CDE-containing mRNAs were identified as the primary targets of Roquin on a transcriptome-wide scale. Thus, Roquin proteins act broadly as mediators of mRNA deadenylation by recognizing a conserved class of stem-loop RNA degradation motifs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Cell Line
  • Humans
  • Inflammation / metabolism
  • Macrophages / metabolism*
  • Mice
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Nucleotide Motifs
  • RNA Stability*
  • RNA, Messenger / chemistry
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Tumor Necrosis Factor-alpha / genetics*
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • 3' Untranslated Regions
  • RNA, Messenger
  • Repressor Proteins
  • Tumor Necrosis Factor-alpha
  • roquin-2 protein, mouse
  • Rc3h1 protein, mouse
  • Ubiquitin-Protein Ligases

Associated data

  • GEO/GSE44775