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Rehage, N. ; Davydova, E.-O. ; Conrad, C.* ; Behrens, G.* ; Maiser, A.* ; Stehklein, J.E. ; Brenner, S. ; Klein, J.* ; Jeridi, A. ; Hoffmann, A.L.* ; Lee, E.* ; Dianzani, U.* ; Willemsen, R.* ; Feederle, R. ; Reiche, K.* ; Hackermüller, J.* ; Leonhardt, H.* ; Sharma, S.* ; Niessing, D. ; Heissmeyer, V.

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

Nat. Commun. 9:299 (2018)
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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 similar to 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Constitutive-decay Element; Mental-retardation Protein; Tfh-cell-differentiation; Helper T-cells; Inducible Costimulator; Dependent Decay; Stress Granule; Stem-loop; B-cells; Autoimmunity
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 9, Issue: 1, Pages: , Article Number: 299 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Immune Regulation (AMIR)
Institute of Structural Biology (STB)
CF Monoclonal Antibodies (CF-MAB)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30201 - Metabolic Health
Research field(s) Immune Response and Infection
Enabling and Novel Technologies
Helmholtz Diabetes Center
PSP Element(s) G-501712-001
G-503091-001
G-502210-001
DOI 10.1038/s41467-017-02582-1
WOS ID WOS:000422911900003
Scopus ID 85040949581
PubMed ID 29352114
Erfassungsdatum 2018-02-28
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