HuR- dependent regulation of mRNA splicing is essential for the B cell antibody response
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Felix Krueger
PROVIDER: E-GEOD-62148 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Post-transcriptional regulation of mRNA by the RNA binding protein HuR is required in B cells for the germinal centre reaction and for the production of class-switched antibodies in response to T-independent antigens. Transcriptome-wide examination of RNA isoforms, abundance and translation in HuR-deficient B cells, together with direct measurements of HuR-RNA interaction, revealed that HuR-dependent mRNA splicing affects hundreds of transcripts including the dihydrolipoyl succinyltransferase (Dlst), a subunit of the aketoglutaratedehydrogenase (aKGDH) enzyme. In the absence of HuR, defective mitochondrial metabolism results in high levels of reactive oxygen species and B cell death. Our study shows how post-transcriptional processes control the balance of energy metabolism required for B cell proliferation and differentiation. Sequencing analysis of ribosome protected RNA fragments in ex vivo or LPS-activated splenic B cells was performed using ARTseqM-bM-^DM-" Ribosome Profiling Kit - Mammalian (Epicentre, RPHMR12126) and Illumina platform. Splenic B cells come from HuRf/f control or HuR cKO mice. 4-5 biological replicates per genotype and condition.
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