Cytoplasmic RNase III Drosha controls lipogenesis by noncanonical regulation of SREBP1

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.