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Bataclan, M.* ; Leoni, C.* ; Moro, S.G.* ; Pecoraro, M.* ; Wong, E.H.* ; Heissmeyer, V. ; Monticelli, S.*

Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression.

Life Sci. All. 7:e202402784 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Post-transcriptional regulation of immune-related transcripts by RNA-binding proteins (RBPs) impacts immune cell responses, including mast cell functionality. Despite their importance in immune regulation, the functional role of most RBPs remains to be understood. By manipulating the expression of specific RBPs in murine mast cells, coupled with mass spectrometry and transcriptomic analyses, we found that the Regnase family of proteins acts as a potent regulator of mast cell physiology. Specifically, Regnase-1 is required to maintain basic cell proliferation and survival, whereas both Regnase-1 and -3 cooperatively regulate the expression of inflammatory transcripts upon activation, with Tnf being a primary target in both human and mouse cells. Furthermore, Regnase-3 directly interacts with Regnase-1 in mast cells and is necessary to restrain Regnase-1 expression through the destabilization of its transcript. Overall, our study identifies protein interactors of endogenously expressed Regnase factors, characterizes the regulatory interplay between Regnase family members in mast cells, and establishes their role in the control of mast cell homeostasis and inflammatory responses.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Rna-binding Proteins; Au-rich Elements; Messenger-rna; Immune-responses; Tnf-alpha; T-cells; Roquin; Degradation; Database; Cleavage
ISSN (print) / ISBN 2575-1077
e-ISSN 2575-1077
Journal Life Science Alliance
Quellenangaben Volume: 7, Issue: 8, Pages: , Article Number: e202402784 Supplement: ,
Publisher EMBO Press
Publishing Place Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Abteilung für Molekulare Immunregulation (AMIR)
Grants Aldo and Cele Dacco Foundation
Swiss National Science Foundation