Journal article

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

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

Nature Immunology | NATURE PUBLISHING GROUP | Published : 2015

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..

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University of Melbourne Researchers

Grants

Awarded by Biotechnology and Biological Sciences Research Council (BBSRC)


Awarded by National Health and Medical Research Council of Australia


Awarded by Russian Science Foundation


Awarded by Slovenian Research Agency


Awarded by Biotechnology and Biological Sciences Research Council


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

We thank K. Bates, D. Sanger, N. Evans, S. Walker, K. Tabbada, G. Morgan, R. Walker and the Babraham Institute Biological Support Unit for technical assistance. Supported by the Biotechnology and Biological Sciences Research Council (BBSRC BB/J001457/1 and BB/J00152X/1), the National Health and Medical Research Council of Australia (516786 to K.F.), the Victorian State Government Operational Infrastructure Support and Australian Government (National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme; K.F.), the European Molecular Biology Laboratory (EMBL Interdisciplinary Postdocs initiative fellowship to. K.Z.), the Russian Science Foundation (14-15-00133 to V.I.B. for work with the phosphonate analogs of 2-oxo acids) and the Slovenian Research Agency (J7-5460 for J.U. and T.C.).