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

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

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)
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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 languageEnglish
Pages (from-to)415-25
Number of pages11
JournalNature Immunology
Volume16
Early online date23 Feb 2015
DOIs
Publication statusPublished - 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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