Protein arginine methyltransferase 5 sustains Tip60-EP400 complex via SRSF1 in Merkel cell carcinoma.

ABSTRACT: Protein arginine methyltransferase 5 (PRMT5) is a key regulator of gene expression and RNA splicing, with therapeutic potential demonstrated in MTAP-deleted cancers. Emerging evidence suggests that MYC-driven tumors or tumors with wild-type TP53 may also be sensitive to PRMT5 inhibition, though the underlying mechanisms remain unclear. Virus-positive Merkel cell carcinoma serves as an ideal model to explore this, as it is driven by the MYC paralog MYCL and retains wild-type TP53 In this study, we examined how PRMT5 regulates the Tip60-EP400 complex, which is recruited by MYCL in Merkel cell carcinoma. Using RNA-seq, we characterized PRMT5-mediated gene expression, whereas Iso-Seq enabled in-depth analysis of PRMT5-mediated alternative splicing. How PRMT5 deficiency selectively affects cert

SUBMITTER: Sevigny JL 

PROVIDER: S-EPMC12373721 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature