The RNA-binding Protein HuR is Required for Maintenance of the Germinal Centre Response
Overview
Authors
Affiliations
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.
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.
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.
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.