» Articles » PMID: 34772950

The RNA-binding Protein HuR is Required for Maintenance of the Germinal Centre Response

Overview
Journal Nat Commun
Specialty Biology
Date 2021 Nov 13
PMID 34772950
Citations 11
Authors
Affiliations
Soon will be listed here.
Abstract

The germinal centre (GC) is required for the generation of high affinity antibodies and immunological memory. Here we show that the RNA binding protein HuR has an essential function in GC B cells to sustain the GC response. In its absence, the GC reaction and production of high-affinity antibody is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively. The expression and splicing patterns of hundreds of genes are altered in the absence of HuR. Among these genes, HuR is required for the expression of Myc and a Myc-dependent transcriptional program that controls GC B cell proliferation and Ig somatic hypermutation. Additionally, HuR regulates the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle, and it modulates a gene signature associated with DNA deamination protecting GC B cells from DNA damage and cell death.

Citing Articles

Critical and differential roles of eIF4A1 and eIF4A2 in B-cell development and function.

Du Y, Xie J, Liu D, Zhao J, Chen P, He X Cell Mol Immunol. 2024; 22(1):40-53.

PMID: 39516355 PMC: 11685474. DOI: 10.1038/s41423-024-01234-x.


Novel, soluble 3-heteroaryl-substituted tanshinone mimics attenuate the inflammatory response in murine macrophages.

Facen E, Assoni G, Donati G, Paladino D, Carreira A, Bonomo I Sci Rep. 2024; 14(1):24501.

PMID: 39424621 PMC: 11489580. DOI: 10.1038/s41598-024-73309-8.


Alternative splicing of ALDOA confers tamoxifen resistance in breast cancer.

Yu S, Wu R, Si Y, Fan Z, Wang Y, Yao C Oncogene. 2024; 43(39):2901-2913.

PMID: 39164523 DOI: 10.1038/s41388-024-03134-w.


Fibroblast-Specific Depletion of Human Antigen R Alleviates Myocardial Fibrosis Induced by Cardiac Stress.

Patil M, Singh S, Dubey P, Tousif S, Umbarkar P, Zhang Q JACC Basic Transl Sci. 2024; 9(6):754-770.

PMID: 39070272 PMC: 11282885. DOI: 10.1016/j.jacbts.2024.03.004.


Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation.

Subramani P, Fraszczak J, Helness A, Estall J, Moroy T, Di Noia J EMBO Rep. 2024; 25(6):2662-2697.

PMID: 38744970 PMC: 11169469. DOI: 10.1038/s44319-024-00152-3.


References
1.
Mesin L, Ersching J, Victora G . Germinal Center B Cell Dynamics. Immunity. 2016; 45(3):471-482. PMC: 5123673. DOI: 10.1016/j.immuni.2016.09.001. View

2.
Liu Y, Zhang J, Lane P, Chan E, MacLennan I . Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens. Eur J Immunol. 1991; 21(12):2951-62. DOI: 10.1002/eji.1830211209. View

3.
Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T . Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000; 102(5):553-63. DOI: 10.1016/s0092-8674(00)00078-7. View

4.
Gitlin A, Mayer C, Oliveira T, Shulman Z, Jones M, Koren A . HUMORAL IMMUNITY. T cell help controls the speed of the cell cycle in germinal center B cells. Science. 2015; 349(6248):643-6. PMC: 4809261. DOI: 10.1126/science.aac4919. View

5.
Shulman Z, Gitlin A, Weinstein J, Lainez B, Esplugues E, Flavell R . Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science. 2014; 345(6200):1058-62. PMC: 4519234. DOI: 10.1126/science.1257861. View