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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Leppek, Kathrin (VerfasserIn) , Schott, Johanna (VerfasserIn) , Reitter, Sonja (VerfasserIn) , Poetz, Fabian (VerfasserIn) , Hammond, Ming C. (VerfasserIn) , Stoecklin, Georg (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: May 9, 2013
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
Volltext
Verfasserangaben:Kathrin Leppek, Johanna Schott, Sonja Reitter, Fabian Poetz, Ming C. Hammond, and Georg Stoecklin
Beschreibung
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.
Beschreibung:Gesehen am 25.01.2022
Beschreibung:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2013.04.016