ALYREF condensation stabilizes m⁵C-modified PARP10 mRNA and promotes PI3K-AKT signaling in ovarian cancer.

ABSTRACT: The role of epigenetic regulation of RNAs in the tumorigenesis remains incompletely understood. This study uncovers a critical function of the 5-methylcytosine (m⁵C) RNA modification reader protein ALYREF (also termed, ALY; BEF) in ovarian cancer. ALYREF is elevated in ovarian cancer patient samples, and its depletion reduces ovarian tumorigenesis and metastasis in mice in a m⁵C-dependent manner. Mechanistically, ALYREF binds to the m⁵C-modified mRNA of ADP-ribosyltransferase PARP10, competing with exosome complex component MTR4, and enhancing the stability and nuclear export of PARP10 mRNA. Further, ALYREF forms condensates in the nucleus of ovarian cancer cells, and depletion or mutation of ALYREF's intrinsically disordered regions rescues its control on

SUBMITTER: Zhao H 

PROVIDER: S-EPMC12811383 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature