Splicing factor 3B subunit 3 (SF3B3) (SF3B3)

Splicing factor 3B subunit 3 (SF3B3), also known as SAP130, is a core component of the SF3B complex, which is an essential part of the U2 small nuclear ribonucleoprotein (snRNP) involved in pre-mRNA splicing (UniProt Q15393). It plays a critical role in the early stages of spliceosome assembly by helping to stabilize the interaction between the U2 snRNP and the branch point sequence of the intron (PubMed: 10323865). Beyond its role in splicing, SF3B3 is also a member of the STAGA transcription coactivator-complex, linking mRNA processing with chromatin remodeling and transcriptional regulation (PubMed: 11564863). In oncology, SF3B3 is frequently overexpressed and serves as a prognostic marker in several malignancies, including breast and liver cancers, where it promotes cell proliferation and survival by modulating the splicing of key oncogenic transcripts (PubMed: 25851150). It has been identified as a potential therapeutic target because its depletion or inhibition leads to significant alterations in alternative splicing and reduced tumor growth (PubMed: 28431239). While most small-molecule splicing inhibitors like E7107 and pladienolides primarily bind to the SF3B1 subunit, SF3B3 is an integral structural and functional member of the targeted SF3B complex (PubMed: 17510415). Disruption of SF3B3 function results in the accumulation of unspliced pre-mRNAs and the induction of apoptosis in cancer cells, making it a focus for developing next-generation spliceosome modulators. Additionally, SF3B3 acts as a damage-associated molecular pattern (DAMP) when released from necrotic cells, interacting with the Mincle receptor to trigger inflammatory responses (PubMed: 18480830). Overall, SF3B3 represents a multifaceted target at the intersection of RNA processing, gene expression, and cancer progression.

Other names

SAP130SF3b130STAF130Spliceosome-associated protein 130

Inhibition of the SF3B complex within the U2 snRNP, leading to the disruption of branch point recognition and modulation of alternative splicing.