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Chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing

Author

Listed:
  • Jian Liu

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Capital Medical University)

  • Chunxiao Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jinsong Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Dongkui Xu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Haijuan Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ting Wang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lina Li

    (Capital Medical University)

  • Hui Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Peng Nan

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jingyao Zhang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yang Wang

    (Dalian Medical University)

  • Changzhi Huang

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Dong Chen

    (ABLife Inc)

  • Yi Zhang

    (ABLife Inc)

  • Tao Wen

    (Capital Medical University)

  • Qimin Zhan

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Peking University Cancer Hospital & Institute)

  • Fei Ma

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Haili Qian

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Dysregulated alternative splicing (AS) driving carcinogenetic mitosis remains poorly understood. Here, we demonstrate that cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, broadly interacts and co-expresses with RBPs across cancers, contributing to cancerous mitosis-related AS. Using developed fCLIP-seq technology, we show that MTA1 binds abundant transcripts, preferentially at splicing-responsible motifs, influencing the abundance and AS pattern of target transcripts. MTA1 regulates the mRNA level and guides the AS of a series of mitosis regulators. MTA1 deletion abrogated the dynamic AS switches of variants for ATRX and MYBL2 at mitotic stage, which are relevant to mitosis-related tumorigenesis. MTA1 dysfunction causes defective mitotic arrest, leads to aberrant chromosome segregation, and results in chromosomal instability (CIN), eventually contributing to tumorigenesis. Currently, little is known about the RNA splicing during mitosis; here, we uncover that MTA1 binds transcripts and orchestrates dynamic splicing of mitosis regulators in tumorigenesis.

Suggested Citation

  • Jian Liu & Chunxiao Li & Jinsong Wang & Dongkui Xu & Haijuan Wang & Ting Wang & Lina Li & Hui Li & Peng Nan & Jingyao Zhang & Yang Wang & Changzhi Huang & Dong Chen & Yi Zhang & Tao Wen & Qimin Zhan &, 2020. "Chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18259-1
    DOI: 10.1038/s41467-020-18259-1
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