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Cryo-EM Structures of Human Drosha and DGCR8 in Complex with Primary MicroRNA.
Molecular Cell ( IF 14.5 ) Pub Date : 2020-03-27 , DOI: 10.1016/j.molcel.2020.02.016
Alexander C Partin 1 , Kaiming Zhang 2 , Byung-Cheon Jeong 1 , Emily Herrell 1 , Shanshan Li 2 , Wah Chiu 3 , Yunsun Nam 1
Affiliation  

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.

中文翻译:

人类Drosha和DGCR8与初级MicroRNA配合的低温EM结构。

后生动物的microRNA需要由微处理器(包括Drosha和DGCR8)启动的特定成熟步骤。缺少用于组装的复合物的结构信息阻碍了对微处理器如何识别初级microRNA转录本(pri-miRNA)的理解。在这里,我们介绍了人类微处理器的低温电子显微镜结构,其中pri-miRNA停靠在活性位点中,准备进行切割。基底交界处由Drosha中的四向分子内交界处识别,该交界处由夹在ssRNA上的Belt和Wedge区域触发。该传送带对于pri-miRNA加工的效率和准确性很重要。两个dsRBD形成分子标尺,以测量两个dsRNA-ssRNA连接之间的茎长。顶端连接附近的dsRBD的具体组织独立于Drosha核心域,如在第二结构中以部分对接状态观察到的。我们共同得出一个分子模型来解释微处理器如何识别pri-miRNA并准确识别切割位点。
更新日期:2020-03-27
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