We have been studying the structure and mechanism of RNA exosome complex using single particle cryo-EM in the past ten years. We solved the cryo-EM structure of hDicer in complex with its cofactor protein TRBP and revealed the precise spatial arrangement of hDicer’s multiple domains. We further solved structures of the hDicer-TRBP complex bound with pre-let-7 RNA in two distinct conformations. In combination with biochemical analysis, these structures reveal a property of the hDicer-TRBP complex to promote the stability of pre-miRNA’s stem duplex in a predicting state. These results provide insights into the mechanism of RNA processing by hDicer and illustrate the regulatory role of hDicer’s N-terminal helicase domain.
Liu Z, Wang J, Cheng H, Ke X, Sun L, Zhang QC, Wang HW*. (2018) Cryo-EM Structure of Human Dicer and Its Complexes with a Pre-miRNA Substrate. Cell, 173(5): 1191-1203 (*corresponding author)