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Effect of SRSF2-P95H mutation on mRNA splicing in primary human hematopoietic stem cells (HSPCs).

ABSTRACT: SRSF2 is a component of the splicing machinery that binds to exonic splicing enhancers (ESE), thus playing an important role in regulation of exon inclusion and exon skipping events during splicing. Mutations in SRSF2 change the binding affinity to specific ESE sequences and thereby lead to missplicing of pre-mRNAs from a plethora of genes. Mutations in SRSF2 occur in several myeloid hematologic malignancies of stem cell origin (CMML, AML) and also in individuals with clonal hematopoiesis. To prospectively analyze splicing alterations induced by SRSF2 mutations, we introduced heterozygous SRSF2-P95H mutations in primary CD34+ HSPCs using CRISPR/Cas9 and rAAV6-mediated knock-in and subjected these cells to bulk RNA sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE304636 | GEO | 2026/09/21

REPOSITORIES: GEO

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Disease-associated mutation in SRSF2 misregulates splicing by altering RNA binding affinities

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