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Nat Immunol. 2015 Apr;16(4):415-25. doi: 10.1038/ni.3115. Epub 2015 Feb 23.

The RNA-binding protein HuR is essential for the B cell antibody response.

Author information

1
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
2
1] Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK. [2] The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
3
MRC Centre for Immune Regulation, Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
4
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.
5
Bioinformatics Group, The Babraham Institute, Cambridge, UK.
6
A. N. Belozersky Institute of PhysicoChemical Biology and Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
7
Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany.
8
University of Ljubljana, Faculty of Computer and Information Science, Ljubljana, Slovenia.
9
Center for Molecular and Vascular Biology, KU Leuven, Belgium.
10
1] Center for Molecular and Vascular Biology, KU Leuven, Belgium. [2] Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
11
Weill Cornell Medical College, Brain and Mind Research Institute, Burke Medical Research Institute, White Plains, New York, USA.
12
Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece.
13
UCL Genetics Institute, Department of Genetics, Environment and Evolution, University College London, London, UK.

Abstract

Post-transcriptional regulation of mRNA by the RNA-binding protein HuR (encoded by Elavl1) is required in B cells for the germinal center reaction and for the production of class-switched antibodies in response to thymus-independent antigens. Transcriptome-wide examination of RNA isoforms and their abundance and translation in HuR-deficient B cells, together with direct measurements of HuR-RNA interactions, revealed that HuR-dependent splicing of mRNA affected hundreds of transcripts, including that encoding dihydrolipoamide S-succinyltransferase (Dlst), a subunit of the 2-oxoglutarate dehydrogenase (α-KGDH) complex. In the absence of HuR, defective mitochondrial metabolism resulted in large amounts of reactive oxygen species and B cell death. Our study shows how post-transcriptional processes control the balance of energy metabolism required for the proliferation and differentiation of B cells.

PMID:
25706746
PMCID:
PMC4479220
DOI:
10.1038/ni.3115
[Indexed for MEDLINE]
Free PMC Article

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