Summary information and primary citation

PDB-id
6lxd; SNAP-derived features in text and JSON formats; DNAproDB
Class
hydrolase-RNA binding protein-RNA
Method
cryo-EM (3.9 Å)
Summary
Pri-mirna bound drosha-dgcr8 complex
Reference
Jin W, Wang J, Liu CP, Wang HW, Xu RM (2020): "Structural Basis for pri-miRNA Recognition by Drosha." Mol.Cell, 78, 423. doi: 10.1016/j.molcel.2020.02.024.
Abstract
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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