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Nat Commun. 2018 Jan 19;9(1):299. doi: 10.1038/s41467-017-02582-1.

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

Author information

1
Institute for Immunology at the Biomedical Center, Ludwig-Maximilians-Universität München, Grosshaderner Strasse 9, 82152, Planegg-Martinsried, Germany.
2
Research Unit Molecular Immune Regulation, Helmholtz Zentrum München, Marchioninistrasse 25, 81377, München, Germany.
3
Group Intracellular Transport and RNA Biology, Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.
4
Center for Integrated Protein Science at the Department of Biology, Ludwig-Maximilians-Universität München, Grosshaderner Strasse 2, 82152, Planegg-Martinsried, Germany.
5
Young Investigators Group Bioinformatics and Transcriptomics, Department Molecular Systems Biology, Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318, Leipzig, Germany.
6
Bioinformatics Group, Department of Computer Science; and Interdisciplinary Center of Bioinformatics, Leipzig University, Härtelstraße 16-18, 04107, Leipzig, Germany.
7
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA.
8
The Functional Genomics Center, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA.
9
Department of Health Sciences, Universita' del Piemonte Orientale, via Solaroli 17, 28100, Novara, Italy.
10
CBG Department of Clinical Genetics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, Netherlands.
11
Monoclonal Antibody Core Facility and Research Group, Institute for Diabetes and Obesity, Helmholtz Zentrum München, Marchioninistrasse 25, 81377, München, Germany.
12
Bioinformatic Unit, Department of Diagnostics, Fraunhofer Institute for Cell Therapy and Immunology- IZI, 04103, Leipzig, Germany.
13
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA. soniasharma@lji.org.
14
The Functional Genomics Center, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA. soniasharma@lji.org.
15
Group Intracellular Transport and RNA Biology, Institute of Structural Biology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany. dierk.niessing@uni-ulm.de.
16
Department of Cell Biology at the Biomedical Center, Ludwig-Maximilians-Universität München, Grosshaderner Strasse 9, 82152, Planegg-Martinsried, Germany. dierk.niessing@uni-ulm.de.
17
Institute of Pharmaceutical Biotechnology, Ulm University, James Franck Ring N27, 89081, Ulm, Germany. dierk.niessing@uni-ulm.de.
18
Institute for Immunology at the Biomedical Center, Ludwig-Maximilians-Universität München, Grosshaderner Strasse 9, 82152, Planegg-Martinsried, Germany. vigo.heissmeyer@med.uni-muenchen.de.
19
Research Unit Molecular Immune Regulation, Helmholtz Zentrum München, Marchioninistrasse 25, 81377, München, Germany. vigo.heissmeyer@med.uni-muenchen.de.

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.

PMID:
29352114
PMCID:
PMC5775257
DOI:
10.1038/s41467-017-02582-1
[Indexed for MEDLINE]
Free PMC Article

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