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Science. 2018 Nov 9;362(6415). pii: eaat6678. doi: 10.1126/science.aat6678. Epub 2018 Sep 27.

Structural insight into precursor tRNA processing by yeast ribonuclease P.

Lan P1, Tan M2,3, Zhang Y4, Niu S2,3,5, Chen J1, Shi S1, Qiu S6, Wang X6, Peng X4, Cai G6, Cheng H2, Wu J7, Li G8, Lei M7,9,10,11.

Author information

1
Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China.
2
State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), Shanghai 200031, China.
3
University of Chinese Academy of Sciences, CAS, Shanghai 200031, China.
4
Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, CAS, Dalian 116023, China.
5
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
6
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
7
Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China. leim@shsmu.edu.cn ghli@dicp.ac.cn wujian@shsmu.edu.cn.
8
Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, CAS, Dalian 116023, China. leim@shsmu.edu.cn ghli@dicp.ac.cn wujian@shsmu.edu.cn.
9
Key laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
10
National Facility for Protein Science in Shanghai, Zhangjiang Laboratory, Shanghai, 201210, China.
11
Shanghai Science Research Center, CAS, Shanghai, 201204, China.

Abstract

Ribonuclease P (RNase P) is a universal ribozyme responsible for processing the 5'-leader of pre-transfer RNA (pre-tRNA). Here, we report the 3.5-angstrom cryo-electron microscopy structures of Saccharomyces cerevisiae RNase P alone and in complex with pre-tRNAPhe The protein components form a hook-shaped architecture that wraps around the RNA and stabilizes RNase P into a "measuring device" with two fixed anchors that recognize the L-shaped pre-tRNA. A universally conserved uridine nucleobase and phosphate backbone in the catalytic center together with the scissile phosphate and the O3' leaving group of pre-tRNA jointly coordinate two catalytic magnesium ions. Binding of pre-tRNA induces a conformational change in the catalytic center that is required for catalysis. Moreover, simulation analysis suggests a two-metal-ion SN2 reaction pathway of pre-tRNA cleavage. These results not only reveal the architecture of yeast RNase P but also provide a molecular basis of how the 5'-leader of pre-tRNA is processed by eukaryotic RNase P.

PMID:
30262633
DOI:
10.1126/science.aat6678
[Indexed for MEDLINE]

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