A transfer-RNA-derived small RNA regulates ribosome biogenesis

Hak Kyun Kim, Gabriele Fuchs, Shengchun Wang, Wei Wei, Yue Zhang, Hyesuk Park, Biswajoy Roy-Chaudhuri, Pan Li, Jianpeng Xu, Kirk Chu, Feijie Zhang, Mei-Sze Chua, Samuel So, Qiangfeng Cliff Zhang, Peter Sarnow and Mark A. Kay ()
Additional contact information
Hak Kyun Kim: Stanford University
Gabriele Fuchs: Stanford University
Shengchun Wang: Stanford University
Wei Wei: Asian Liver Center, Stanford University School of Medicine
Yue Zhang: Stanford University
Hyesuk Park: Stanford University
Biswajoy Roy-Chaudhuri: Stanford University
Pan Li: MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University
Jianpeng Xu: Stanford University
Kirk Chu: Stanford University
Feijie Zhang: Stanford University
Mei-Sze Chua: Asian Liver Center, Stanford University School of Medicine
Samuel So: Asian Liver Center, Stanford University School of Medicine
Qiangfeng Cliff Zhang: MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University
Peter Sarnow: Stanford University
Mark A. Kay: Stanford University

Nature, 2017, vol. 552, issue 7683, 57-62

Abstract: Abstract Transfer-RNA-derived small RNAs (tsRNAs; also called tRNA-derived fragments) are an abundant class of small non-coding RNAs whose biological roles are not well understood. Here we show that inhibition of a specific tsRNA, LeuCAG3′tsRNA, induces apoptosis in rapidly dividing cells in vitro and in a patient-derived orthotopic hepatocellular carcinoma model in mice. This tsRNA binds at least two ribosomal protein mRNAs (RPS28 and RPS15) to enhance their translation. A decrease in translation of RPS28 mRNA blocks pre-18S ribosomal RNA processing, resulting in a reduction in the number of 40S ribosomal subunits. These data establish a post-transcriptional mechanism that can fine-tune gene expression during different physiological states and provide a potential new target for treating cancer.

Date: 2017
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DOI: 10.1038/nature25005

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