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RNA-binding proteins control the G2-M checkpoint of the germinal center B cell [RNAseq]

GSE279999 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/10/24 Platform GPL24247
Summary
The germinal center (GC) reaction drives the production of high-affinity antibodies by iterative cycles of B cell somatic hypermutation, selection, and proliferation. How GC B cells undergo rapid cell division while maintaining genome stability is poorly understood. Here, we show that the RNA binding proteins ZFP36L1 and ZFP36L2 act downstream of antigen sensing and protect GC B cells from replication stress by controlling a cell cycle-related posttranscriptional regulon. They safeguard the successful completion of mitosis by balancing CDK1 and p21-mediated regulation of cell-cycle progression. In their absence, GC B cells are prone to arrest in the G2-M phase and die by apoptosis, resulting in curtailed GC responses. DNA replication forks stalled at active replication initiation zones, causing replication stress and increased activity of the ATR-CHK1 DNA damage response. Thus, RNA binding proteins guide posttranscriptional gene regulation and maintain a functional G2-M checkpoint in GC B cells.
Published in
RNA binding proteins control the G(2)-M checkpoint of the germinal center B cell
Salerno F, Whale AJ, Matheson LS et al. · Science immunology 2025 · PMID 41171880 · doi:10.1126/sciimmunol.adu3718
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Also filed as BioProject PRJNA1175714 and SRA study SRP539995. Searching any of these in the dataset finder brings you back here.

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