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


ABSTRACT: The multifunctional RNA-binding protein hnRNPL has been implicated in antibody class switching but its broader function in B cells is unknown. Here, we show that hnRNPL is essential for B cell activation, germinal center, and antibody responses. Upon activation, hnRNPL-deficient B cells show proliferation defects and increased apoptosis. Comparative analysis of RNA-seq data from activated B cells and another 8 hnRNPL-depleted cell types reveals a common effect on the MYC and E2F transcriptional programs required for proliferation. Notably, while individual gene expression changes were cell type specific, several alternative splicing events affecting histone modifiers like KDM6A and SIRT1, were conserved across cell types. Moreover, hnRNPL-deficient B cells showed global changes in H3K27me3 and H3K9ac. Epigenetic dysregulation after hnRNPL loss could underlie differential gene expression and upregulation of lncRNAs, and explain common and cell type-specific phenotypes, such as dysfunctional mitochondria and ROS overproduction in mouse B cells. Thus, hnRNPL is essential for the resting-to-activated B cell transition by regulating transcriptional programs and metabolism, at least in part through the alternative splicing of several histone modifiers.

ORGANISM(S): Mus musculus (mouse)

SUBMITTER:  

PROVIDER: S-BSST1365 | biostudies-other |

SECONDARY ACCESSION(S): GSE242069

REPOSITORIES: biostudies-other

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