Journal
MOLECULAR CELL
Volume 78, Issue 3, Pages 423-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2020.02.024
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Funding
- Natural Science Foundation of China [31521002, 31700721, 31825009]
- Ministry of Science and Technology of China [2019YFA0508900, 2016YFA0501100]
- Beijing Municipal Science and Technology Project [Z171100000417001]
- Youth Innovation Promotion Association of CAS [2018125]
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A commencing and critical step in miRNA biogenesis involves processing of pri-miRNAs in the nucleus by Microprocessor. An important, but not completely understood, question is how Drosha, the catalytic subunit of Microprocessor, binds pri-miRNAs and correctly specifies cleavage sites. Here we report the cryoelectron microscopy structures of the Drosha-DGCR8 complex with and without a pri-miRNA. The RNA-bound structure provides direct visualization of the tertiary structure of pri-miRNA and shows that a helix hairpin in the extended PAZ domain and the mobile basic (MB) helix in the RNase Illa domain of Drosha coordinate to recognize the single-stranded to double-stranded junction of RNA, whereas the dsRNA binding domain makes extensive contacts with the RNA stem. Furthermore, the RNA-free structure reveals an autoinhibitory conformation of the PAZ helix hairpin. These findings provide mechanistic insights into pri-miRNA cleavage site selection and conformational dynamics governing pri-miRNA recognition by the catalytic component of Microprocessor.
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