A transfer-RNA-derived small RNA regulates ribosome biogenesis

作者:Kim, Hak Kyun; Fuchs, Gabriele; Wang, Shengchun; Wei, Wei; Zhang, Yue; Park, Hyesuk; Roy-Chaudhuri, Biswajoy; Li, Pan; Xu, Jianpeng; Chu, Kirk; Zhang, Feijie; Chua, Mei-Sze; So, Samuel; Zhang, Qiangfeng Cliff; Sarnow, Peter; Kay, Mark A.*
来源:Nature, 2017, 552(7683): 57-+.
DOI:10.1038/nature25005

摘要

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.