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最新重要论文(影响因子PNAS及以上)

Structural Basis for pri-miRNA Recognition by Drosha, Mol Cell, 27 Mar 2020

发布时间:2020年03月27日

Molecular Cell27 March, 2020,DOI:

Structural Basis for pri-miRNA Recognition by Drosha

Wenxing Jin, Jia Wang, Chao-Pei Liu, Hong-Wei Wang, Rui-Ming Xu

Summary

明朝登陆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.

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