一种源自转运RNA的小RNA调控核糖体生物合成。

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

Department of Pediatrics, Stanford University, Stanford, California 94305, USA.

Department of Genetics, Stanford University, Stanford, California 94305, USA.

Nature. 2017 Dec 7;552(7683):57-62. doi: 10.1038/nature25005. Epub 2017 Nov 29.

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.

转运RNA衍生的小RNA（tsRNAs；也称为tRNA衍生片段）是一类丰富的小非编码RNA，其生物学功能尚不清楚。我们在此表明，抑制特定的tsRNA，即亮氨酸CAG 3' tsRNA，可在体外快速分裂细胞以及小鼠患者源性原位肝细胞癌模型中诱导细胞凋亡。这种tsRNA与至少两种核糖体蛋白mRNA（RPS28和RPS15）结合，以增强它们的翻译。RPS28 mRNA翻译的减少会阻断前18S核糖体RNA的加工，导致40S核糖体亚基数量减少。这些数据建立了一种转录后机制，该机制可在不同生理状态下微调基因表达，并为癌症治疗提供了一个潜在的新靶点。