The RNA-binding protein HuR is essential for the B cell antibody response
- Author(s)
- Diaz-Munoz, 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;
- Details
- Publication Year 2015-04,Volume 16,Issue #4,Page 415-425
- Journal Title
- Nat Immunol
- Publication Type
- Journal Article
- 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 (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.
- Publisher
- NPG
- Research Division(s)
- Molecular Medicine
- Publisher's Version
- https://doi.org/10.1038/ni.3115
- NHMRC Grants
- NHMRC/516786,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-02-25 01:47:25
Last Modified: 2015-05-21 11:51:11