Cryo-EM Structure of Human Dicer and Its Complexes with a Pre-miRNA Substrate

Publication date: Available online 26 April 2018 Source:Cell Author(s): Zhongmin Liu, Jia Wang, Hang Cheng, Xin Ke, Lei Sun, Qiangfeng Cliff Zhang, Hong-Wei Wang Human Dicer (hDicer) is a multi-domain protein belonging to the RNase III family. It plays pivotal roles in small RNA biogenesis during the RNA interference (RNAi) pathway by processing a diverse range of double-stranded RNA (dsRNA) precursors to generate ∼22 nt microRNA (miRNA) or small interfering RNA (siRNA) products for sequence-directed gene silencing. In this work, we solved the cryoelectron microscopy (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 pre-dicing 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. Graphical abstract Teaser Structural analysis of human Dicer shows how it collaborates with an accessory protein to position a pre-miRNA substrate for processing.

Source: Cell - April 27, 2018 Category: Cytology Source Type: research