2026-10-12T14:00:48Z https://data.mendeley.com/oai

oai:data.mendeley.com/4n7tfpt4zs.2 2026-04-28T17:03:14Z

Nie, Tiejian Cytoplasmic RNase III Drosha controls lipogenesis by noncanonical regulation of SREBP1 Mendeley Data RNase III Drosha initiates miRNA biogenesis. Emerging evidence suggests that Drosha modulate other processes beyond miRNA biogenesis, indicative of a functional complexity of Drosha. Here we show that Drosha facilitates activation of sterol regulatory element-binding protein 1 (SREBP1), the central player in triglycerides (TG) biosynthesis, in a RNase activity-independent manner. Mechanistically, cytoplasmic Drosha interacts with Sec31, a subunit of COPII, through its RS-rich domain. This interaction promotes COPII-mediated transportation of SREBP1 from endoplasmic reticulum to Golgi where it is proteolytically activated. Moreover, Akt phosphorylates Drosha at Ser237 in RS-rich domain, which is required for Drosha-Sec31 interaction, SREBP1 processing and TG accumulation in response to insulin. The Akt-Drosha-SREBP1 axis was hyperactivated in obese mice, and hepatic Drosha deletion or administration of an interfering peptide that blocked Akt-mediated phosphorylation of Drosha ameliorate liver TG deposition and insulin resistance. Thus, our findings uncover a noncanonical function of Drosha involved SREBP1 processing and lipogenesis. Metabolism Lipogenesis Dataset doi:10.17632/4n7tfpt4zs.2 oai:data.mendeley.com/4n7tfpt4zs.2 Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 https://data.mendeley.com/datasets/4n7tfpt4zs 2026-04-28T17:03:14Z