Summary information and primary citation
- PDB-id
- 5zam; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- hydrolase-protein binding-RNA
- Method
- cryo-EM (5.7 Å)
- Summary
- cryo-EM structure of human dicer and its complexes with a pre-mirna substrate
- Reference
- 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, 1191-1203.e12. doi: 10.1016/j.cell.2018.03.080.
- Abstract
- 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.
