Structural Basis for pri-miRNA Recognition by Drosha.,Molecular Cell

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Structural Basis for pri-miRNA Recognition by Drosha.
Molecular Cell ( IF 14.5 ) Pub Date : 2020-03-27 , DOI: 10.1016/j.molcel.2020.02.024
Wenxing Jin ₁ , Jia Wang ₂ , Chao-Pei Liu ₁ , Hong-Wei Wang ₂ , Rui-Ming Xu ₃

Affiliation

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.

中文翻译：

Drosha识别pri-miRNA的结构基础。

miRNA生物发生中的一个关键开始步骤是通过微处理器处理pri-miRNA在细胞核中。一个重要但尚未完全理解的问题是微处理器的催化亚基Drosha如何结合pri-miRNA并正确指定切割位点。在这里，我们报告了Drosha-DGCR8复合体在有和没有pri-miRNA的情况下的低温电子显微镜结构。RNA结合的结构提供pri-miRNA的三级结构的直接可视化，并显示扩展的PAZ域中的螺旋发夹和Drosha RNase IIIa域中的移动碱性（MB）螺旋协同识别单链氨基酸。 RNA的双链连接，而dsRNA结合结构域则与RNA茎广泛接触。此外，无RNA的结构揭示了PAZ螺旋发夹的自抑制构象。这些发现提供了对pri-miRNA裂解位点选择和构象动力学的机制性见解，从而控制了微处理器催化成分对pri-miRNA的识别。

更新日期：2020-03-27

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