Author
Listed:
- Nina Rehage
(Ludwig-Maximilians-Universität München
Helmholtz Zentrum München)
- Elena Davydova
(Helmholtz Zentrum München)
- Christine Conrad
(Ludwig-Maximilians-Universität München)
- Gesine Behrens
(Ludwig-Maximilians-Universität München)
- Andreas Maiser
(Ludwig-Maximilians-Universität München)
- Jenny E. Stehklein
(Helmholtz Zentrum München)
- Sven Brenner
(Helmholtz Zentrum München)
- Juliane Klein
(Ludwig-Maximilians-Universität München)
- Aicha Jeridi
(Helmholtz Zentrum München)
- Anne Hoffmann
(Helmholtz Centre for Environmental Research – UFZ
Leipzig University)
- Eunhae Lee
(La Jolla Institute for Allergy and Immunology
La Jolla Institute for Allergy and Immunology)
- Umberto Dianzani
(Universita’ del Piemonte Orientale)
- Rob Willemsen
(Erasmus MC)
- Regina Feederle
(Helmholtz Zentrum München)
- Kristin Reiche
(Fraunhofer Institute for Cell Therapy and Immunology- IZI)
- Jörg Hackermüller
(Helmholtz Centre for Environmental Research – UFZ)
- Heinrich Leonhardt
(Ludwig-Maximilians-Universität München)
- Sonia Sharma
(La Jolla Institute for Allergy and Immunology
La Jolla Institute for Allergy and Immunology)
- Dierk Niessing
(Helmholtz Zentrum München
Ludwig-Maximilians-Universität München
Ulm University)
- Vigo Heissmeyer
(Ludwig-Maximilians-Universität München
Helmholtz Zentrum München)
Abstract
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.
Suggested Citation
Nina Rehage & Elena Davydova & Christine Conrad & Gesine Behrens & Andreas Maiser & Jenny E. Stehklein & Sven Brenner & Juliane Klein & Aicha Jeridi & Anne Hoffmann & Eunhae Lee & Umberto Dianzani & R, 2018.
"Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA,"
Nature Communications, Nature, vol. 9(1), pages 1-15, December.
Handle:
RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02582-1
DOI: 10.1038/s41467-017-02582-1
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