Journal
NATURE
Volume 552, Issue 7683, Pages 57-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature25005
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Funding
- National Institutes of Health [R01AI071068, R01DK114483]
- Stanford Cancer Institute
- CJ Huang Foundation
- TS Kwok Liver Cancer Foundation
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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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