Roquin Promotes Constitutive mRNA Decay via a Conserved Class of Stem-Loop Recognition Motifs
|Authors:||Leppek K, Schott J, Reitter S, Poetz F, Hammond MC, Stoecklin G|
|CellNetworks People:||Stoecklin Georg|
|Journal:||Cell, Volume 153, Issue 4, 869-881, 9 May 2013, 10.1016/j.cell.2013.04.016|
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.