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 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.
Mesh Terms:
3' Untranslated Regions, Animals, Base Sequence, Cell Line, Humans, Inflammation, Macrophages, Mice, Molecular Sequence Data, Nucleic Acid Conformation, Nucleotide Motifs, RNA Stability, RNA, Messenger, Repressor Proteins, Sequence Alignment, Tumor Necrosis Factor-alpha, Ubiquitin-Protein Ligases
3' Untranslated Regions, Animals, Base Sequence, Cell Line, Humans, Inflammation, Macrophages, Mice, Molecular Sequence Data, Nucleic Acid Conformation, Nucleotide Motifs, RNA Stability, RNA, Messenger, Repressor Proteins, Sequence Alignment, Tumor Necrosis Factor-alpha, Ubiquitin-Protein Ligases
Cell
Date: May. 09, 2013
PubMed ID: 23663784
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