The RNA-binding protein HuR is essential for the B cell antibody response.
Nat Immunol
; 16(4): 415-25, 2015 Apr.
Article
in 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.
Full text:
1
Database:
MEDLINE
Main subject:
Immunoglobulins
/
RNA, Messenger
/
B-Lymphocytes
/
Germinal Center
/
ELAV Proteins
/
Immunity, Humoral
Limits:
Animals
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2015
Type:
Article
Affiliation country:
United kingdom