The RNA-binding protein HuR is essential for the B cell antibody response.
Nat Immunol
; 16(4): 415-25, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25706746
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulinas
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RNA Mensageiro
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Linfócitos B
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Centro Germinativo
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Proteínas ELAV
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Imunidade Humoral
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article