Molecular Cell, 27 March, 2020，DOI:
Structural Basis for pri-miRNA Recognition by Drosha
北京快乐8玩法wenxing jin, jia wang, chao-pei liu, hong-wei wang, rui-ming xu
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.