A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature Kim, H. K., Fuchs, G. n., Wang, S. n., Wei, W. n., Zhang, Y. n., Park, H. n., Roy-Chaudhuri, B. n., Li, P. n., Xu, J. n., Chu, K. n., Zhang, F. n., Chua, M. S., So, S. n., Zhang, Q. C., Sarnow, P. n., Kay, M. A. 2017; 552 (7683): 57–62


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.

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