title: The RNA-binding protein HuR is essential for the B cell antibody response.
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.
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Diaz-Muñoz
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bell
authors.affiliation: 1] Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK. [2] The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fairfax
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Elisa
authors.initials: E
authors.lastname: Monzon-Casanova
authors.affiliation: MRC Centre for Immune Regulation, Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.
authors.forename: Mar
authors.initials: M
authors.lastname: Gonzalez-Porta
authors.affiliation: Bioinformatics Group, The Babraham Institute, Cambridge, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Andrews
authors.affiliation: A. N. Belozersky Institute of PhysicoChemical Biology and Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Victoria I
authors.initials: VI
authors.lastname: Bunik
authors.affiliation: Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany.
authors.forename: Kathi
authors.initials: K
authors.lastname: Zarnack
authors.affiliation: University of Ljubljana, Faculty of Computer and Information Science, Ljubljana, Slovenia.
authors.forename: Tomaž
authors.initials: T
authors.lastname: Curk
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Belgium.
authors.forename: Ward A
authors.initials: WA
authors.lastname: Heggermont
authors.affiliation: 1] Center for Molecular and Vascular Biology, KU Leuven, Belgium. [2] Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
authors.forename: Stephane
authors.initials: S
authors.lastname: Heymans
authors.affiliation: Weill Cornell Medical College, Brain and Mind Research Institute, Burke Medical Research Institute, White Plains, New York, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Gibson
authors.affiliation: Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Vari, Greece.
authors.forename: Dimitris L
authors.initials: DL
authors.lastname: Kontoyiannis
authors.affiliation: UCL Genetics Institute, Department of Genetics, Environment and Evolution, University College London, London, UK.
authors.forename: Jernej
authors.identifier: 0000000224524277
authors.initials: J
authors.lastname: Ule
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
authors.forename: Martin
authors.identifier: 0000000238019896
authors.initials: M
authors.lastname: Turner
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology; D017398:Alternative Splicing / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016923:Cell Death; D002454:Cell Differentiation; D049109:Cell Proliferation; D051959:ELAV Proteins / Q000235:genetics / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D056724:Immunity, Humoral; D007114:Immunization; D017578:Immunoglobulin Class Switching; D007136:Immunoglobulins / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D012756:Sheep
chemical_list: D000941:Antigens; D051959:ELAV Proteins; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000217:Acyltransferases; C021515:dihydrolipoamide succinyltransferase