State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510060, Guangdong, China.
Nat Commun. 2018 Mar 21;9(1):1165. 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.
剪接转移（t）RNA 和核糖体（r）RNA 是细胞克服各种环境压力的翻译调控的关键且保守步骤。然而，在高等真核生物中，负责这一事件的酶尚未被完全鉴定。在这里，我们报告了一种哺乳动物 tRNA/rRNA 靶向内切核糖核酸酶：SLFN13，它是 Schlafen 家族的一员。结构研究揭示了 SLFN13 N'-结构域独特的伪二聚体 U 形枕头状结构，可能夹在碱基配对的 RNA 上。SLFN13 能够在体外消化 tRNA 和 rRNA，内切核酸酶切割在接受茎处从 tRNA 的 3'-末端切断 11 个核苷酸。细胞质定位的 SLFN13 抑制 293T 细胞中的蛋白质合成。此外，SLFN13 以依赖核酶活性的方式限制 HIV 复制。根据这些观察结果，我们将 SLFN13 命名为 RNase S13。我们的研究为高等真核生物中翻译机制的调节提供了新的见解，并揭示了 Schlafen 家族的功能机制。
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