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HERO ID
4308371
Reference Type
Journal Article
Title
The RNA-binding protein HuR is essential for the B cell antibody response
Author(s)
Diaz-Muñoz, MD; Bell, SE; Fairfax, K; Monzon-Casanova, E; Cunningham, AF; Gonzalez-Porta, M; Andrews, SR; Bunik, VI; Zarnack, K; Curk, T; Heggermont, WA; Heymans, S; Gibson, GE; Kontoyiannis, DL; Ule, J; Turner, M
Year
2015
Is Peer Reviewed?
1
Journal
Nature Immunology
ISSN:
1529-2908
EISSN:
1529-2916
Volume
16
Issue
4
Page Numbers
415-425
Language
English
PMID
25706746
DOI
10.1038/ni.3115
Web of Science Id
WOS:000351333700014
URL
http://www.nature.com/articles/ni.3115
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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.
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