2. Academic Validation
  3. Structure of Schlafen13 reveals a new class of tRNA/rRNA- targeting RNase engaged in translational control

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

  • Nat Commun. 2018 Mar 21;9(1):1165. doi: 10.1038/s41467-018-03544-x.
Jin-Yu Yang 1,  Xiang-Yu Deng 2,  Yi-Sheng Li 3 4,  Xian-Cai Ma 5,  Jian-Xiong Feng 1,  Bing Yu 1,  Yang Chen 1 6,  Yi-Ling Luo 1,  Xi Wang 3 7,  Mei-Ling Chen 1,  Zhi-Xin Fang 1,  Fu-Xiang Zheng 5,  Yi-Ping Li 5,  Qian Zhong 1,  Tie-Bang Kang 1,  Li-Bing Song 1,  Rui-Hua Xu 1,  Mu-Sheng Zeng 1,  Wei Chen 4 8,  Hui Zhang 5,  Wei Xie 9,  Song Gao 10
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • 2 State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510060, Guangdong, China.
  • 3 Laboratory for Functional Genomics and Systems Biology, Berlin Institute for Medical Systems Biology, Berlin, 13125, Germany.
  • 4 Department of Biology, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
  • 5 Key Laboratory of Tropical Disease Control of Ministry of Education, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.
  • 6 Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, 20892, USA.
  • 7 Division of Theoretical Systems Biology, German Cancer Research Center, Heidelberg, 69120, Germany.
  • 8 Medi-X Institute, SUSTech Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.
  • 9 State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510060, Guangdong, China. [email protected].
  • 10 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China. [email protected].
PMID: 29563550 DOI: 10.1038/s41467-018-03544-x
Abstract

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.

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