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134803 - The RNA-binding protein HuR is essential for the B cell antibody response.pdf (3.5 MB)

The RNA-binding protein HuR (Elavl1) is essential for the B cell antibody response

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posted on 2023-05-20, 06:57 authored by Diaz-Munoz, MD, Bell, SE, Kirsten FairfaxKirsten Fairfax, Monzon-Casanova, E, Cunningham, AF, Gonzalez-Porta, M, Andrews, SR, Bunik, VI, Zarnack, K, Curk, T, Heggermont, WA, Heymans, S, Gibson, GE, Kontoyiannis, DL, Ule, J, Turner, M
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.

History

Publication title

Nature Immunology

Volume

16

Issue

4

Pagination

415-425

ISSN

1529-2908

Department/School

Menzies Institute for Medical Research

Publisher

Nature Publishing Group

Place of publication

345 Park Ave South, New York, USA, Ny, 10010-1707

Rights statement

Copyright 2015 the authors. Post-prints are subject to Springer Nature re-use terms

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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