Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T17 differentiation
Details
Publication Year 2014-10-05, Volume 15, Issue #11, Page 1079-1089
Journal Title
Nat Immunol
Publication Type
Journal Article
Abstract
Humoral autoimmunity paralleled by the accumulation of follicular helper T cells (TFH cells) is linked to mutation of the gene encoding the RNA-binding protein roquin-1. Here we found that T cells lacking roquin caused pathology in the lung and accumulated as cells of the TH17 subset of helper T cells in the lungs. Roquin inhibited TH17 cell differentiation and acted together with the endoribonuclease regnase-1 to repress target mRNA encoding the TH17 cell-promoting factors IL-6, ICOS, c-Rel, IRF4, IkappaBNS and IkappaBzeta. This cooperation required binding of RNA by roquin and the nuclease activity of regnase-1. Upon recognition of antigen by the T cell antigen receptor (TCR), roquin and regnase-1 proteins were cleaved by the paracaspase MALT1. Thus, this pathway acts as a 'rheostat' by translating TCR signal strength via graded inactivation of post-transcriptional repressors and differential derepression of targets to enhance TH17 differentiation.
Publisher
NPG
WEHI Research Division(s)
Molecular Immunology
Publisher's Version
https://doi.org/10.1038/ni.3008
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2014-10-13 02:21:50
Last Modified: 2015-09-29 03:29:40
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