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

doi:10.1038/ni.3115

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 (alpha-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.

Original language	English
Pages (from-to)	415-425
Journal	Nature Immunology
Volume	16
Issue number	4
DOIs	https://doi.org/10.1038/ni.3115
Publication status	Published - Apr 2015

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Diaz-Munoz, M. D., Bell, S. E., Fairfax, K., Monzon-Casanova, E., Cunningham, A. F., Gonzalez-Porta, M., Andrews, S. R., Bunik, V. I., Zarnack, K., Curk, T., Heggermont, W. A., Heymans, S., Gibson, G. E., Kontoyiannis, D. L., Ule, J., & Turner, M. (2015). The RNA-binding protein HuR is essential for the B cell antibody response. Nature Immunology, 16(4), 415-425. https://doi.org/10.1038/ni.3115

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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 (alpha-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.",

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

year = "2015",

month = apr,

doi = "10.1038/ni.3115",

language = "English",

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pages = "415--425",

journal = "Nature Immunology",

issn = "1529-2908",

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Diaz-Munoz, MD, Bell, SE, Fairfax, K, 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 2015, 'The RNA-binding protein HuR is essential for the B cell antibody response', Nature Immunology, vol. 16, no. 4, pp. 415-425. https://doi.org/10.1038/ni.3115

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AU - Diaz-Munoz, Manuel D.

AU - Bell, Sarah E.

AU - Fairfax, Kirsten

AU - Monzon-Casanova, Elisa

AU - Cunningham, Adam F.

AU - Gonzalez-Porta, Mar

AU - Andrews, Simon R.

AU - Bunik, Victoria I.

AU - Zarnack, Kathi

AU - Curk, Tomaz

AU - Heggermont, Ward A.

AU - Heymans, Stephane

AU - Gibson, Gary E.

AU - Kontoyiannis, Dimitris L.

AU - Ule, Jernej

AU - Turner, Martin

PY - 2015/4

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AB - 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 (alpha-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.

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