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4308371 
Journal Article 
The RNA-binding protein HuR is essential for the B cell antibody response 
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 
2015 
Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916 
16 
415-425 
English 
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.