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Publication : Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA.

First Author  Rehage N Year  2018
Journal  Nat Commun Volume  9
Issue  1 Pages  299
PubMed ID  29352114 Mgi Jnum  J:258592
Mgi Id  MGI:6114906 Doi  10.1038/s41467-017-02582-1
Citation  Rehage N, et al. (2018) Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA. Nat Commun 9(1):299
abstractText  The ubiquitously expressed RNA-binding proteins Roquin-1 and Roquin-2 are essential for appropriate immune cell function and postnatal survival of mice. Roquin proteins repress target mRNAs by recognizing secondary structures in their 3''-UTRs and by inducing mRNA decay. However, it is unknown if other cellular proteins contribute to target control. To identify cofactors of Roquin, we used RNA interference to screen ~1500 genes involved in RNA-binding or mRNA degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA decay. NUFIP2 binds directly and with high affinity to Roquin, which stabilizes NUFIP2 in cells. Post-transcriptional repression of human ICOS by endogenous Roquin proteins requires two neighboring non-canonical stem-loops in the ICOS 3''-UTR. This unconventional cis-element as well as another tandem loop known to confer Roquin-mediated regulation of the Ox40 3''-UTR, are bound cooperatively by Roquin and NUFIP2. NUFIP2 therefore emerges as a cofactor that contributes to mRNA target recognition by Roquin.
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