biostudies-literatureQin FNatural Science Foundation of Chongqing (Natural Science Foundation of Chongqing Municipality)National Natural Science Foundation of China (National Science Foundation of China)4828https://www.ebi.ac.uk/biostudies/studies/S-EPMC12103590biostudies-literatureUnknown16(1)Ovarian cancer has the highest mortality rate among gynecologic tumors worldwide, with unclear underlying mechanisms of pathogenesis. RNA-binding proteins (RBPs) primarily direct post-transcriptional regulation through modulating RNA metabolism. Recent evidence demonstrates that RBPs are also implicated in transcriptional control. However, the role and mechanism of RBP-mediated transcriptional regulation in tumorigenesis remain largely unexplored. Here, we show that the RBP heterogeneous ribonucleoprotein L (hnRNPL) interacts with chromatin and regulates gene transcription by forming phase-separated condensates in ovarian cancer. hnRNPL phase separation activates PIK3CB transcription and glycolysis, thus promoting ovarian cancer progression. Notably, we observe that the PIK3CB promoter is Nature communicationshnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer.PMC12103590321011648227315682072886CSTB2023NSCQ-MSX0338CSTB2022NSCQ-MSX0897Cheng CRen YZuo XLuo FYi PWang HYang DLiu TYang CXu JLiu XLuo QYang YWei QQin FWang WLuo XWang YTang YfalsehnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer.Ovarian cancer has the highest mortality rate among gynecologic tumors worldwide, with unclear underlying mechanisms of pathogenesis. RNA-binding proteins (RBPs) primarily direct post-transcriptional regulation through modulating RNA metabolism. Recent evidence demonstrates that RBPs are also implicated in transcriptional control. However, the role and mechanism of RBP-mediated transcriptional regulation in tumorigenesis remain largely unexplored. Here, we show that the RBP heterogeneous ribonucleoprotein L (hnRNPL) interacts with chromatin and regulates gene transcription by forming phase-separated condensates in ovarian cancer. hnRNPL phase separation activates PIK3CB transcription and glycolysis, thus promoting ovarian cancer progression. Notably, we observe that the PIK3CB promoter is 2025-01-01T00:00:00Z2025 May2026-06-02T02:42:19.736Z2026-04-13T03:12:25.485ZS-EPMC121035904041318910.1038/s41467-025-60115-7