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Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs

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 m...

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Main Authors: Leppek, Kathrin (Author) , Schott, Johanna (Author) , Reitter, Sonja (Author) , Poetz, Fabian (Author) , Hammond, Ming C. (Author) , Stoecklin, Georg (Author)
Format: Article (Journal)
Language:English
Published: May 9, 2013
In: Cell
Year: 2013, Volume: 153, Issue: 4, Pages: 869-881
ISSN:1097-4172
DOI:10.1016/j.cell.2013.04.016
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cell.2013.04.016
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867413004571
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Author Notes:Kathrin Leppek, Johanna Schott, Sonja Reitter, Fabian Poetz, Ming C. Hammond, and Georg Stoecklin

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520 |a 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. 
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