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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 (alpha-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.
Original languageEnglish
Pages (from-to)415-425
JournalNature Immunology
Issue number4
Publication statusPublished - Apr 2015


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