RNA-binding proteins rewire transcriptomes during immune cell differentiation

Alternative PolyAdenylation (APA), is used by >70% of genes in human and has emerged as a major mechanism for the diversification of their transcriptomes and regulation of gene expression. We are investigating APA in individual cell types focusing on the immune system, specifically CD8+ T cells that respond to virus infections, which comprises a complex mix of cell subtypes at various stages of differentiation. We predicted a set of trans-acting RNA binding proteins (RBPs) that are important in T cell differentiation from the pattern of APA in their transcriptomes. We combine single-cell assays, CRISPR gene knockouts in transgenic CD8+ T cells, computational analysis and machine learning models to understand the functional and phenotypic implications of new roles of trans-acting RBPs in regulating APA in the immune system.

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