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Regnase-1 and roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms

Item Type:Article
Title:Regnase-1 and roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms
Creators Name:Mino, T. and Murakawa, Y. and Fukao, A. and Vandenbon, A. and Wessels, H.H. and Ori, D. and Uehata, T. and Tartey, S. and Akira, S. and Suzuki, Y. and Vinuesa, C.G. and Ohler, U. and Standley, D.M. and Landthaler, M. and Fujiwara, T. and Takeuchi, O.
Abstract:Regnase-1 and Roquin are RNA binding proteins essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. However, their mechanistic relationship has yet to be clarified. Here, we show that, although Regnase-1 and Roquin regulate an overlapping set of mRNAs via a common stem-loop structure, they function in distinct subcellular locations: ribosome/endoplasmic reticulum and processing-body/stress granules, respectively. Moreover, Regnase-1 specifically cleaves and degrades translationally active mRNAs and requires the helicase activity of UPF1, similar to the decay mechanisms of nonsense mRNAs. In contrast, Roquin controls translationally inactive mRNAs, independent of UPF1. Defects in both Regnase-1 and Roquin lead to large increases in their target mRNAs, although Regnase-1 tends to control the early phase of inflammation when mRNAs are more actively translated. Our findings reveal that differential regulation of mRNAs by Regnase-1 and Roquin depends on their translation status and enables elaborate control of inflammation.
Keywords:Base Sequence, HeLa Cells, Inflammation, Messenger RNA, Molecular Sequence Data, NIH 3T3 Cells, Nucleic Acid Conformation, Polyribosomes, Protein Biosynthesis, RNA Stability, Ribonucleases, Ribosomal Proteins, Terminator Codon, Trans-Activators, Ubiquitin-Protein Ligases, Animals, Mice
Source:Cell
ISSN:0092-8674
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:161
Number:5
Page Range:1058-1073
Date:21 May 2015
Official Publication:https://doi.org/10.1016/j.cell.2015.04.029
PubMed:View item in PubMed

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