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Effect of SRSF1 splicing factor knockdown in the physiology and function of cytotoxic CD8 T lymphocytes and a potential molecular mechanism in viral immunopathogenesis

ABSTRACT: Cytotoxic CD8 T cells are crucial for the host antigen-specific immune response to viral pathogens. Here we report the identification of an essential role for the serine/arginine-rich splicing factor (SRSF) 1 in CD8 T cell homeostasis and function Transcriptomics analyses of Srsf1-deficient T cells reveal that SRSF1 controls cell cycle, MAP kinase signaling and IFN signaling pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE201028 | GEO | 2022/07/31

REPOSITORIES: GEO

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PAR-CLIP analysis of YTHDC1, SRSF1, SRSF3, SRSF7, SRSF9 and SRSF10 in human HeLa cells

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Targeting PRMT1-mediated SRSF1 Methylation to Suppress Exon Inclusion within Oncogenic Transcripts and Breast Tumorigenesis

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Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy

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SRSF1-mediated alternative splicing is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition [LACE-seq]

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SRSF1-mediated alternative splicing is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition [RNA-Seq]

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Project description:Alternative splicing generates distinct mRNA variants and is essential for development, homeostasis, and renewal. Proteins of the serine/arginine (SR)-rich splicing factor family are major splicing regulators that are broadly required for organ development as well as cell and organism viability. However, how these proteins support adult organ function remains largely unknown. Here, we used the continuously growing mouse incisor as a model to dissect the functions of the prototypical SR-family protein SRSF1 during tissue homeostasis and renewal. We identified an SRSF1-governed alternative splicing network that is specifically required for dental proliferation and survival of progenitors but dispensable for the viability of differentiated cells. We also observed a similar progenitor-specific role of SRSF1 in the small intestinal epithelium, indicating a conserved function of SRSF1 across adult epithelial tissues. Thus, our findings define a regulatory mechanism by which SRSF1 specifically controls progenitor-specific alternative splicing events to support adult tissue homeostasis and renewal.

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