Splicing factor 3B subunit 1 (SF3B1) (SF3B1)

Splicing factor 3B subunit 1 (SF3B1) is a critical protein component of the U2 snRNP complex, essential for the recognition of the branch point sequence during the early stages of pre-mRNA splicing. It is the most commonly mutated splicing factor across various cancers, with high frequencies in myelodysplastic syndromes, chronic lymphocytic leukemia, and uveal melanoma. These mutations cause the spliceosome to utilize incorrect branch points, leading to widespread alternative splicing and the production of novel, cancer-specific mRNA isoforms. These aberrant transcripts can encode neoantigens that are presented on the cell surface, providing a unique opportunity for targeted immunotherapy. Pharmacological targeting of SF3B1 with small molecules like H3B-8800 exploits the dependency of mutant cells on the remaining wild-type splicing activity, leading to selective apoptosis of tumor cells.

Other names

SAP155SF3B155Splicing factor 3b subunit 1Pre-mRNA-splicing factor SF3b 155 kDa subunit

Small molecule inhibition of the SF3b complex to induce lethal mis-splicing in mutant cells; generation of splicing-derived neoantigens for immunotherapy.