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Title | Cryo-EM Structure of Human Dicer and Its Complexes with a Pre-miRNA Substrate. |
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Journal, issue, pages | Cell, Vol. 173, Issue 5, Page 1191-1203.e12, Year 2018 |
Publish date | May 17, 2018 |
Authors | Zhongmin Liu / Jia Wang / Hang Cheng / Xin Ke / Lei Sun / Qiangfeng Cliff Zhang / Hong-Wei Wang / |
PubMed 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 ...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. |
External links | Cell / PubMed:29706542 |
Methods | EM (single particle) |
Resolution | 4.4 - 5.7 Å |
Structure data | EMDB-6904, PDB-5zak: |
Source |
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Keywords | HYDROLASE/PROTEIN BINDING / Dicer / TRBP / Cryo-EM / RNA interference / HYDROLASE-PROTEIN BINDING complex / HYDROLASE/PROTEIN BINDING/RNA / PROTEIN BINDING / HYDROLASE-PROTEIN BINDING-RNA complex |