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TitleCryo-EM Structure of Human Dicer and Its Complexes with a Pre-miRNA Substrate.
Journal, issue, pagesCell, Vol. 173, Issue 5, Page 1191-1203.e12, Year 2018
Publish dateMay 17, 2018
AuthorsZhongmin Liu / Jia Wang / Hang Cheng / Xin Ke / Lei Sun / Qiangfeng Cliff Zhang / Hong-Wei Wang /
PubMed AbstractHuman 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 linksCell / PubMed:29706542
MethodsEM (single particle)
Resolution4.4 - 5.7 Å
Structure data

6904

5zak

EMDB-6904, PDB-5zak:
Cryo-EM structure of human Dicer and its complexes with a pre-miRNA substrate
Method: EM (single particle) / Resolution: 4.4 Å

6905

5zal

EMDB-6905, PDB-5zal:
Cryo-EM structure of human Dicer and its complexes with a pre-miRNA substrate
Method: EM (single particle) / Resolution: 4.7 Å

6906

5zam

EMDB-6906, PDB-5zam:
Cryo-EM structure of human Dicer and its complexes with a pre-miRNA substrate
Method: EM (single particle) / Resolution: 5.7 Å

Source
  • homo sapiens (human)
KeywordsHYDROLASE/PROTEIN BINDING / Dicer / TRBP / Cryo-EM / RNA interference / HYDROLASE-PROTEIN BINDING complex / HYDROLASE/PROTEIN BINDING/RNA / PROTEIN BINDING / HYDROLASE-PROTEIN BINDING-RNA complex

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