Elucidating the molecular mechanisms of SF3B2 in HNSCC

Splicing factor 3b subunit 2 (SF3B2, also known as SAP145 and SF3b145) is a component of the SF3b complex assembled into the U2 snRNP complex. SF3B2 has a role in the U2 snRNP complex to splice intron from pre-mRNA. Besides, SF3B2 directly interacts with RNA sequence coding cryptic exon and increases in expression of a splicing variant that promotes tumor malignancy in castration-resistant prostate cancer (CRPC). High SF3B2 expression is associated with poor prognosis at least in prostate cancer, bladder cancer, acute myeloid leukemia (AML), lung adenocarcinoma, breast cancer, and head and neck squamous cell carcinoma (HNSCC). Thus, SF3B2 has a distinct role in RNA splicing from that in the U2 snRNP complex, and its high expression contributes to promoting tumor malignancy. In the present study, we revealed that SF3B2 regulates transcription with SMC1A, a cohesin component, and CTCF parallel with RNA splicing regulation. SF3B2 differently interacted with genome and RNA. SF3B2 promoted SMC1A loading on SF3B2-binding genomic elements and was associated with suppressing CTCF-mediated activation of transcription.