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The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth

Author

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  • Dongmei Bai

    (State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    School of Life Sciences, Peking University)

  • Jinfang Zhang

    (State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    School of Life Sciences, Peking University)

  • Tingting Li

    (State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    School of Life Sciences, Peking University)

  • Runlai Hang

    (State key Laboratory of Plant Genetics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
    College of Life Sciences, University of the Chinese Academy of Sciences)

  • Yong Liu

    (State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    School of Life Sciences, Peking University)

  • Yonglu Tian

    (School of Life Sciences, Peking University)

  • Dadu Huang

    (School of Life Sciences, Peking University)

  • Linglong Qu

    (State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    School of Life Sciences, Peking University)

  • Xiaofeng Cao

    (State key Laboratory of Plant Genetics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
    College of Life Sciences, University of the Chinese Academy of Sciences)

  • Jiafu Ji

    (Key Laboratory of Carcinogenesis and Translational Research, Peking University Caner Hospital and Institute)

  • Xiaofeng Zheng

    (State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
    School of Life Sciences, Peking University)

Abstract

Dysfunctions in ribosome biogenesis cause developmental defects and increased cancer susceptibility; however, the connection between ribosome assembly and tumorigenesis remains unestablished. Here we show that hCINAP (also named AK6) is required for human 18S rRNA processing and 40S subunit assembly. Homozygous CINAP−/− mice show embryonic lethality. The heterozygotes are viable and show defects in 18S rRNA processing, whereas no delayed cell growth is observed. However, during rapid growth, CINAP haploinsufficiency impairs protein synthesis. Consistently, hCINAP depletion in fast-growing cancer cells inhibits ribosome assembly and abolishes tumorigenesis. These data demonstrate that hCINAP reduction is a specific rate-limiting controller during rapid growth. Notably, hCINAP is highly expressed in cancers and correlated with a worse prognosis. Genome-wide polysome profiling shows that hCINAP selectively modulates cancer-associated translatome to promote malignancy. Our results connect the role of hCINAP in ribosome assembly with tumorigenesis. Modulation of hCINAP expression may be a promising target for cancer therapy.

Suggested Citation

  • Dongmei Bai & Jinfang Zhang & Tingting Li & Runlai Hang & Yong Liu & Yonglu Tian & Dadu Huang & Linglong Qu & Xiaofeng Cao & Jiafu Ji & Xiaofeng Zheng, 2016. "The ATPase hCINAP regulates 18S rRNA processing and is essential for embryogenesis and tumour growth," Nature Communications, Nature, vol. 7(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12310
    DOI: 10.1038/ncomms12310
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