Structural Basis for pri-miRNA Recognition by Drosha
| Autor: | Jia Wang, Wenxing Jin, Rui-Ming Xu, Hong-Wei Wang, Chao-Pei Liu |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Ribonuclease III Protein Conformation DGCR8 RNase P Spodoptera Cleavage (embryo) 03 medical and health sciences 0302 clinical medicine Protein Domains microRNA Animals Humans Molecular Biology Drosha 030304 developmental biology 0303 health sciences biology Cryoelectron Microscopy RNA-Binding Proteins RNA Cell Biology Protein tertiary structure MicroRNAs biology.protein Biophysics 030217 neurology & neurosurgery Alpha helix |
| Zdroj: | Molecular Cell. 78:423-433.e5 |
| ISSN: | 1097-2765 |
| Popis: | 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 IIIa 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. |
| Databáze: | OpenAIRE |
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