Cryo-EM Structure of the Human Ribonuclease P Holoenzyme

Cell. 2018 Nov 15;175(5):1393-1404.e11. doi: 10.1016/j.cell.2018.10.003.

Jian Wu ¹, Shuangshuang Niu ², Ming Tan ³, Chenhui Huang ¹, Mingyue Li ², Yang Song ¹, Qianmin Wang ¹, Juan Chen ¹, Shaohua Shi ¹, Pengfei Lan ⁴, Ming Lei ⁵

Affiliations

1 Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China.
2 CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
3 CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
4 Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China. Electronic address: [email protected].
5 Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China; Key laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai 201210, China; Shanghai Science Research Center, Chinese Academy of Sciences, Shanghai 201204, China. Electronic address: [email protected].

PMID: 30454648 DOI: 10.1016/j.cell.2018.10.003

Abstract

Ribonuclease (RNase) P is a ubiquitous ribozyme that cleaves the 5' leader from precursor tRNAs. Here, we report cryo-electron microscopy structures of the human nuclear RNase P alone and in complex with tRNA^Val. Human RNase P is a large ribonucleoprotein complex that contains 10 protein components and one catalytic RNA. The protein components form an interlocked clamp that stabilizes the RNA in a conformation optimal for substrate binding. Human RNase P recognizes the tRNA using a double-anchor mechanism through both protein-RNA and RNA-RNA interactions. Structural comparison of the apo and tRNA-bound human RNase P reveals that binding of tRNA induces a local conformational change in the catalytic center, transforming the ribozyme into an active state. Our results also provide an evolutionary model depicting how auxiliary RNA elements in Bacterial RNase P, essential for substrate binding, and catalysis, were replaced by the much more complex and multifunctional protein components in higher organisms.

Keywords

RNase P; cryo-EM; ribozyme.

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