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TitleCryo-EM Structures of Human Drosha and DGCR8 in Complex with Primary MicroRNA.
Journal, issue, pagesMol Cell, Vol. 78, Issue 3, Page 411-422.e4, Year 2020
Publish dateMay 7, 2020
AuthorsAlexander C Partin / Kaiming Zhang / Byung-Cheon Jeong / Emily Herrell / Shanshan Li / Wah Chiu / Yunsun Nam /
PubMed AbstractMetazoan microRNAs require specific maturation steps initiated by Microprocessor, comprising Drosha and DGCR8. Lack of structural information for the assembled complex has hindered an understanding ...Metazoan microRNAs require specific maturation steps initiated by Microprocessor, comprising Drosha and DGCR8. Lack of structural information for the assembled complex has hindered an understanding of how Microprocessor recognizes primary microRNA transcripts (pri-miRNAs). Here we present a cryoelectron microscopy structure of human Microprocessor with a pri-miRNA docked in the active site, poised for cleavage. The basal junction is recognized by a four-way intramolecular junction in Drosha, triggered by the Belt and Wedge regions that clamp over the ssRNA. The belt is important for efficiency and accuracy of pri-miRNA processing. Two dsRBDs form a molecular ruler to measure the stem length between the two dsRNA-ssRNA junctions. The specific organization of the dsRBDs near the apical junction is independent of Drosha core domains, as observed in a second structure in the partially docked state. Collectively, we derive a molecular model to explain how Microprocessor recognizes a pri-miRNA and accurately identifies the cleavage site.
External linksMol Cell / PubMed:32220646 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 4.4 Å
Structure data

21051

6v5b

EMDB-21051, PDB-6v5b:
Human Drosha and DGCR8 in complex with Primary MicroRNA (MP/RNA complex) - Active state
Method: EM (single particle) / Resolution: 3.7 Å

21052

6v5c

EMDB-21052, PDB-6v5c:
Human Drosha and DGCR8 in complex with Primary MicroRNA (MP/RNA complex) - partially docked state
Method: EM (single particle) / Resolution: 4.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsRNA BINDING PROTEIN/RNA / Microprocessor / Drosha / DGCR8 / Primary MicroRNA / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA complex

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