Structure of Schlafen13 reveals a new class of tRNA/rRNA- targeting RNase engaged in translational control

• Published in: Nature communications Vol. 9; no. 1; pp. 1165 - 13
• Main Authors: Yang, Jin-Yu, Deng, Xiang-Yu, Li, Yi-Sheng, Ma, Xian-Cai, Feng, Jian-Xiong, Yu, Bing, Chen, Yang, Luo, Yi-Ling, Wang, Xi, Chen, Mei-Ling, Fang, Zhi-Xin, Zheng, Fu-Xiang, Li, Yi-Ping, Zhong, Qian, Kang, Tie-Bang, Song, Li-Bing, Xu, Rui-Hua, Zeng, Mu-Sheng, Chen, Wei, Zhang, Hui, Xie, Wei, Gao, Song
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21-03-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 13/31; 13/89; 14/35; 38/1; 38/70; 38/77; 631/337; 631/45/500; 631/45/607; 631/535/1266; 82/29; 82/80; 82/83; Binding Sites; Cleavage; Cloning, Molecular; Crystallography, X-Ray; Cytoplasm - chemistry; Cytoplasm - enzymology; Cytoplasm - virology; Endoribonucleases - chemistry; Endoribonucleases - genetics; Endoribonucleases - metabolism; Environmental stress; Escherichia coli - genetics; Escherichia coli - metabolism; Eukaryotes; Gene Expression; Genetic Vectors; HEK293 Cells; HIV; HIV-1 - genetics; HIV-1 - growth & development; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Kinetics; Machinery and equipment; Models, Molecular; multidisciplinary; Nucleotides; Protein Binding; Protein Biosynthesis; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein synthesis; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Ribonuclease; Ribonucleic acid; RNA; RNA Cleavage; RNA, Ribosomal - chemistry; RNA, Ribosomal - genetics; RNA, Ribosomal - metabolism; RNA, Transfer - chemistry; RNA, Transfer - genetics; RNA, Transfer - metabolism; rRNA; Science; Science (multidisciplinary); Substrate Specificity; Translation; tRNA; Virus Replication
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03544-x

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.