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IGF2BP3 promotes mRNA degradation through internal m7G modification

Author

Listed:
  • Chang Liu

    (The University of Chicago
    The University of Chicago
    Stanford University)

  • Xiaoyang Dou

    (The University of Chicago
    The University of Chicago)

  • Yutao Zhao

    (The University of Chicago
    The University of Chicago)

  • Linda Zhang

    (The University of Chicago
    The University of Chicago)

  • Lisheng Zhang

    (The University of Chicago
    The University of Chicago
    The Hong Kong University of Science and Technology
    The Hong Kong University of Science and Technology)

  • Qing Dai

    (The University of Chicago
    The University of Chicago)

  • Jun Liu

    (Peking University
    Peking University)

  • Tong Wu

    (The University of Chicago
    The University of Chicago)

  • Yu Xiao

    (The University of Chicago
    The University of Chicago)

  • Chuan He

    (The University of Chicago
    The University of Chicago)

Abstract

Recent studies have suggested that mRNA internal m7G and its writer protein METTL1 are closely related to cell metabolism and cancer regulation. Here, we identify that IGF2BP family proteins IGF2BP1-3 can preferentially bind internal mRNA m7G. Such interactions, especially IGF2BP3 with m7G, could promote the degradation of m7G target transcripts in cancer cells. IGF2BP3 is more responsive to changes of m7G modification, while IGF2BP1 prefers m6A to stabilize the bound transcripts. We also demonstrate that p53 transcript, TP53, is m7G-modified at its 3’UTR in cancer cells. In glioblastoma, the methylation level and the half lifetime of the modified transcript could be modulated by tuning IGF2BP3, or by site-specific targeting of m7G through a dCas13b-guided system, resulting in modulation of cancer progression and chemosensitivity.

Suggested Citation

  • Chang Liu & Xiaoyang Dou & Yutao Zhao & Linda Zhang & Lisheng Zhang & Qing Dai & Jun Liu & Tong Wu & Yu Xiao & Chuan He, 2024. "IGF2BP3 promotes mRNA degradation through internal m7G modification," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51634-w
    DOI: 10.1038/s41467-024-51634-w
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    References listed on IDEAS

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