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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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
May 9, 2013
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| In: |
Cell
Year: 2013, Jahrgang: 153, Heft: 4, Pages: 869-881 |
| ISSN: | 1097-4172 |
| DOI: | 10.1016/j.cell.2013.04.016 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cell.2013.04.016 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867413004571 |
| Verfasserangaben: | Kathrin Leppek, Johanna Schott, Sonja Reitter, Fabian Poetz, Ming C. Hammond, and Georg Stoecklin |
| Zusammenfassung: | 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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| Beschreibung: | Gesehen am 25.01.2022 |
| Beschreibung: | Online Resource |
| ISSN: | 1097-4172 |
| DOI: | 10.1016/j.cell.2013.04.016 |