期刊
NATURE IMMUNOLOGY
卷 16, 期 4, 页码 415-425出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3115
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资金
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J001457/1, BB/J00152X/1]
- National Health and Medical Research Council of Australia [516786]
- Victorian State Government Operational Infrastructure Support
- Australian Government (National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme)
- European Molecular Biology Laboratory (EMBL Interdisciplinary Postdocs initiative fellowship)
- Russian Science Foundation [14-15-00133]
- Slovenian Research Agency [J7-5460]
- Biotechnology and Biological Sciences Research Council [BB/J001457/1, BBS/E/B/000C0409, BB/L009986/1, BB/J00152X/1, BBS/E/B/000C0407] Funding Source: researchfish
- Russian Science Foundation [14-15-00133] Funding Source: Russian Science Foundation
- BBSRC [BB/L009986/1, BB/J00152X/1, BBS/E/B/000C0407, BBS/E/B/000C0409, BB/J001457/1] Funding Source: UKRI
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.
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