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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 (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.
Original language | English |
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Pages (from-to) | 415-25 |
Number of pages | 11 |
Journal | Nature Immunology |
Volume | 16 |
Early online date | 23 Feb 2015 |
DOIs | |
Publication status | Published - Apr 2015 |
Keywords
- Acyltransferases
- Alternative Splicing
- Animals
- Antigens
- B-Lymphocytes
- Cell Death
- Cell Differentiation
- Cell Proliferation
- Erythrocytes
- Germinal Center
- Hu Paraneoplastic Encephalomyelitis Antigens
- Immunity, Humoral
- Immunization
- Immunoglobulin Class Switching
- Immunoglobulins
- Lipopolysaccharides
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mitochondria
- RNA, Messenger
- Reactive Oxygen Species
- Sheep
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Dive into the research topics of 'The RNA-binding protein HuR is essential for the B cell antibody response'. Together they form a unique fingerprint.Projects
- 1 Finished
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How does systemic flagellin immunization induce mucosal lgA?
Cunningham, A. (Principal Investigator) & Toellner, K. (Co-Investigator)
Biotechnology & Biological Sciences Research Council
1/02/14 → 31/01/18
Project: Research Councils