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

• Verfasst von: Leppek, Kathrin [VerfasserIn]
• Verfasst von: Schott, Johanna [VerfasserIn]
• Verfasst von: Reitter, Sonja [VerfasserIn]
• Verfasst von: Poetz, Fabian [VerfasserIn]
• Verfasst von: Hammond, Ming C. [VerfasserIn]
• Verfasst von: Stoecklin, Georg [VerfasserIn]
• Titel: Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs
• Verf.angabe: Kathrin Leppek, Johanna Schott, Sonja Reitter, Fabian Poetz, Ming C. Hammond, and Georg Stoecklin
• E-Jahr: 2013
• Jahr: May 9, 2013
• Umfang: 13 S.
• Fussnoten: Gesehen am 25.01.2022
• Titel Quelle: Enthalten in: Cell
• Ort Quelle: [Cambridge, Mass.] : Cell Press, 1974
• Jahr Quelle: 2013
• Band/Heft Quelle: 153(2013), 4 vom: Mai, Seite 869-881
• ISSN Quelle: 1097-4172
• DOI: doi:10.1016/j.cell.2013.04.016
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1787083748

Abstract

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.