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

Nat Immunol. 2015 Apr;16(4):415-25. doi: 10.1038/ni.3115. Epub 2015 Feb 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / immunology
  • Alternative Splicing / immunology
  • Animals
  • Antigens / administration & dosage
  • Antigens / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • Cell Death
  • Cell Differentiation
  • Cell Proliferation
  • ELAV Proteins / genetics
  • ELAV Proteins / immunology*
  • Erythrocytes / immunology
  • Germinal Center / cytology
  • Germinal Center / drug effects
  • Germinal Center / immunology*
  • Immunity, Humoral*
  • Immunization
  • Immunoglobulin Class Switching
  • Immunoglobulins / biosynthesis*
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / genetics
  • Mitochondria / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology*
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism
  • Sheep

Substances

  • Antigens
  • ELAV Proteins
  • Immunoglobulins
  • Lipopolysaccharides
  • RNA, Messenger
  • Reactive Oxygen Species
  • Acyltransferases
  • dihydrolipoamide succinyltransferase

Associated data

  • GEO/GSE62129
  • GEO/GSE62134
  • GEO/GSE62148