A transfer-RNA-derived small RNA regulates ribosome biogenesis

被引:439
作者
Kim, Hak Kyun [1 ,2 ]
Fuchs, Gabriele [3 ,6 ,7 ]
Wang, Shengchun [1 ,2 ,8 ]
Wei, Wei [4 ]
Zhang, Yue [1 ,2 ,9 ]
Park, Hyesuk [1 ,2 ]
Roy-Chaudhuri, Biswajoy [1 ,2 ,10 ]
Li, Pan [5 ]
Xu, Jianpeng [1 ,2 ]
Chu, Kirk [1 ,2 ]
Zhang, Feijie [1 ,2 ]
Chua, Mei-Sze [4 ]
So, Samuel [4 ]
Zhang, Qiangfeng Cliff [5 ]
Sarnow, Peter [3 ]
Kay, Mark A. [1 ,2 ]
机构
[1] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[4] Stanford Univ, Dept Surg, Asian Liver Ctr, Sch Med, Stanford, CA 94305 USA
[5] Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Ctr Synthet & Syst Biol,MOE Key Lab Bioinformat, Beijing Adv Innovat Ctr Struct Biol,Sch Life Sci, Beijing 100084, Peoples R China
[6] SUNY Albany, RNA Inst, 1400 Washington Ave, Albany, NY 12222 USA
[7] SUNY Albany, Dept Biol Sci, 1400 Washington Ave, Albany, NY 12222 USA
[8] Medtron Vasc, 3576 Unocal Pl, Santa Rosa, CA 95403 USA
[9] Stanford Ctr Genom & Personalized Med, 3165 Porter Dr, Palo Alto, CA 94304 USA
[10] Impossible Foods Inc, 525 Chesapeake Dr, Redwood City, CA 94063 USA
基金
美国国家卫生研究院;
关键词
DIAMOND-BLACKFAN ANEMIA; CELL-PROLIFERATION; NUCLEIC-ACID; FRAGMENTS; REVEALS; GENE; EXPRESSION; PROTEINS; MATURATION; EFFICIENT;
D O I
10.1038/nature25005
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
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.
引用
收藏
页码:57 / +
页数:21
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