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

Manuel D Diaz-Muñoz, Sarah E Bell, Kirsten Fairfax, Elisa Monzon-Casanova, Adam F Cunningham, Mar Gonzalez-Porta, Simon R Andrews, Victoria I Bunik, Kathi Zarnack, Tomaž Curk, Ward A Heggermont, Stephane Heymans, Gary E Gibson, Dimitris L Kontoyiannis, Jernej Ule, Martin Turner

OAI: oai:www.repository.cam.ac.uk:1810/293908 • DOI: 10.17863/CAM.41016

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.

Acyltransferases Alternative Splicing Animals Antigens B-Lymphocytes Cell Death Cell Differentiation Cell Proliferation ELAV Proteins Erythrocytes Germinal Center Immunity Humoral Immunization Immunoglobulin Class Switching Immunoglobulins Lipopolysaccharides Mice Mice Inbred C57BL Mice Knockout Mitochondria RNA Messenger Reactive Oxygen Species Sheep