期刊
CELL
卷 153, 期 4, 页码 869-881出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.04.016
关键词
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资金
- Helmholtz Gemeinschaft [HZ-NG-210]
- Deutsche Forschungsgemeinschaft [SFB 1036/TP07, STO 859/2-1, STO 859/3-1]
- Helmholtz International Graduate School for Cancer Research
- CASI (Career Awards at the Scientific Interface) award from the Burroughs Wellcome Fund
Tumor necrosis factor-alpha (INF-alpha) is the most potent proinflammatory cytokine in mammals. The degradation of TNF-alpha mRNA is critical for restricting TNF-alpha 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-alpha mRNA and limits TNF- alpha 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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