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A transfer-RNA-derived small RNA regulates ribosome biogenesis

Author

Listed:
  • Hak Kyun Kim

    (Stanford University
    Stanford University)

  • Gabriele Fuchs

    (Stanford University
    University at Albany, State University of New York)

  • Shengchun Wang

    (Stanford University
    Stanford University
    Medtronic Vascular)

  • Wei Wei

    (Asian Liver Center, Stanford University School of Medicine)

  • Yue Zhang

    (Stanford University
    Stanford University
    Stanford Center for Genomics and Personalized Medicine)

  • Hyesuk Park

    (Stanford University
    Stanford University)

  • Biswajoy Roy-Chaudhuri

    (Stanford University
    Stanford University
    Impossible Foods Inc.)

  • Pan Li

    (MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Jianpeng Xu

    (Stanford University
    Stanford University)

  • Kirk Chu

    (Stanford University
    Stanford University)

  • Feijie Zhang

    (Stanford University
    Stanford University)

  • Mei-Sze Chua

    (Asian Liver Center, Stanford University School of Medicine)

  • Samuel So

    (Asian Liver Center, Stanford University School of Medicine)

  • Qiangfeng Cliff Zhang

    (MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Peter Sarnow

    (Stanford University)

  • Mark A. Kay

    (Stanford University
    Stanford University)

Abstract

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.

Suggested Citation

  • Hak Kyun Kim & Gabriele Fuchs & Shengchun Wang & Wei Wei & Yue Zhang & Hyesuk Park & Biswajoy Roy-Chaudhuri & Pan Li & Jianpeng Xu & Kirk Chu & Feijie Zhang & Mei-Sze Chua & Samuel So & Qiangfeng Clif, 2017. "A transfer-RNA-derived small RNA regulates ribosome biogenesis," Nature, Nature, vol. 552(7683), pages 57-62, December.
    • Handle: RePEc:nat:nature:v:552:y:2017:i:7683:d:10.1038_nature25005
    DOI: 10.1038/nature25005
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    Cited by:

    1. Hanyong Jin & Ji-Hyun Yeom & Eunkyoung Shin & Yoonjie Ha & Haifeng Liu & Daeyoung Kim & Minju Joo & Yong-Hak Kim & Hak Kyun Kim & Minkyung Ryu & Hong-Man Kim & Jeongkyu Kim & Keun P. Kim & Yoonsoo Hah, 2024. "5′-tRNAGly(GCC) halves generated by IRE1α are linked to the ER stress response," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Zhangli Su & Ida Monshaugen & Briana Wilson & Fengbin Wang & Arne Klungland & Rune Ougland & Anindya Dutta, 2022. "TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Hejin Lai & Ning Feng & Qiwei Zhai, 2023. "Discovery of the major 15–30 nt mammalian small RNAs, their biogenesis and function," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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