남윤선 (University of Texas Southwestern Medical Center) | 한빛사논문 > 한빛사

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University of Texas Southwestern Medical Center

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Mol. Cell, 2020 May 7;78(3):411-422.e4 | https://doi.org/10.1016/j.molcel.2020.02.016 Cryo-EM Structures of Human Drosha and DGCR8 in Complex with Primary MicroRNA

Alexander C. Partin ^1,2,5, Kaiming Zhang^3,5, Byung-Cheon Jeong ^1,2, Emily Herrell ^1,2, Shanshan Li ³, Wah Chiu ^3,4, Yunsun Nam ^1,2,6

¹Laboratory of RNA Biology, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
²Departments of Biophysics and Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
³Department of Bioengineering and James H. Clark Center, Stanford University, Stanford, CA 94305, USA
⁴CryoEM and Bioimaging Division, SSRL, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025, USA
⁵These authors contributed equally
⁶Lead Contact

Corresponding author: Yunsun Nam

Abstract

Metazoan microRNAs require specific maturation steps initiated by Microprocessor, comprising Drosha and DGCR8. Lack of structural information for the assembled complex has hindered an understanding of how Microprocessor recognizes primary microRNA transcripts (pri-miRNAs). Here we present a cryoelectron microscopy structure of human Microprocessor with a pri-miRNA docked in the active site, poised for cleavage. The basal junction is recognized by a four-way intramolecular junction in Drosha, triggered by the Belt and Wedge regions that clamp over the ssRNA. The belt is important for efficiency and accuracy of pri-miRNA processing. Two dsRBDs form a molecular ruler to measure the stem length between the two dsRNA-ssRNA junctions. The specific organization of the dsRBDs near the apical junction is independent of Drosha core domains, as observed in a second structure in the partially docked state. Collectively, we derive a molecular model to explain how Microprocessor recognizes a pri-miRNA and accurately identifies the cleavage site.

논문정보

형식Research article
게재일2020년 05월 (BRIC 등록일 2023-03-16)
연구진국외 연구진
분야 생명과학 > 생화학

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