Structure of Schlafen13 reveals a new class of tRNA/rRNA- targeting RNase engaged in translational control
| Autor: | Xiang Yu Deng, Yi Ling Luo, Jian Xiong Feng, Yang Chen, Wei Xie, Qian Zhong, Mu Sheng Zeng, Xiancai Ma, Mei Ling Chen, Hui Zhang, Tiebang Kang, Fu Xiang Zheng, Zhi Xin Fang, Wei Chen, Bing Yu, Xi Wang, Rui-Hua Xu, Libing Song, Jin Yu Yang, Yi Sheng Li, Song Gao, Yi-Ping Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation alpha-Helical Cancer Research Cytoplasm RNase P Science Endoribonuclease Genetic Vectors General Physics and Astronomy Gene Expression Crystallography X-Ray Virus Replication General Biochemistry Genetics and Molecular Biology Article Substrate Specificity 03 medical and health sciences RNA Transfer Gene expression Endoribonucleases Protein biosynthesis Escherichia coli Humans Protein Interaction Domains and Motifs Cloning Molecular lcsh:Science RNA Cleavage Multidisciplinary Binding Sites Chemistry RNA General Chemistry Ribosomal RNA Recombinant Proteins Cell biology Kinetics 030104 developmental biology HEK293 Cells Cardiovascular and Metabolic Diseases RNA Ribosomal Protein Biosynthesis Transfer RNA HIV-1 Protein Conformation beta-Strand lcsh:Q Technology Platforms Protein Binding |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-03544-x |
| Popis: | Cleavage of transfer (t)RNA and ribosomal (r)RNA are critical and conserved steps of translational control for cells to overcome varied environmental stresses. However, enzymes that are responsible for this event have not been fully identified in high eukaryotes. Here, we report a mammalian tRNA/rRNA-targeting endoribonuclease: SLFN13, a member of the Schlafen family. Structural study reveals a unique pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N′-domain that may clamp base-paired RNAs. SLFN13 is able to digest tRNAs and rRNAs in vitro, and the endonucleolytic cleavage dissevers 11 nucleotides from the 3′-terminus of tRNA at the acceptor stem. The cytoplasmically localised SLFN13 inhibits protein synthesis in 293T cells. Moreover, SLFN13 restricts HIV replication in a nucleolytic activity-dependent manner. According to these observations, we term SLFN13 RNase S13. Our study provides insights into the modulation of translational machinery in high eukaryotes, and sheds light on the functional mechanisms of the Schlafen family. Translation inhibition is a strategy for organisms to overcome various environmental stresses including viral infections. Here the authors show that a tRNA/rRNA-targeting RNase Schlafen13 inhibits protein synthesis by directly digesting cytoplasmic tRNA and rRNA with the ability to restrict viral propagation. |
| Databáze: | OpenAIRE |
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