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

The RNA-binding protein HuR post-transcriptionally regulates mRNA splicing. Turner and colleagues demonstrate that HuR serves a critical role in thymus-independent antigen responses by regulating the fate of genes related to B cell energy use. 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.