Details

Autor(en) / Beteiligte

• Diaz-Muñoz, Manuel D
• Bell, Sarah E
• Fairfax, Kirsten
• Monzon-Casanova, Elisa
• Cunningham, Adam F
• Gonzalez-Porta, Mar
• Andrews, Simon R
• Bunik, Victoria I
• Zarnack, Kathi
• Curk, Tomaž
• Heggermont, Ward A
• Heymans, Stephane
• Gibson, Gary E
• Kontoyiannis, Dimitris L
• Ule, Jernej
• Turner, Martin

Titel

The RNA-binding protein HuR is essential for the B cell antibody response

Ist Teil von

• Nature immunology, 2015-04, Vol.16 (4), p.415-425

Ort / Verlag

United States

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.