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An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis

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  • Song Zhu

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • Ji-Zhong Wang

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • De Chen

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • Yu-Tian He

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • Nan Meng

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • Min Chen

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • Rui-Xun Lu

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • Xin-Hui Chen

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • Xiao-Lan Zhang

    (The Third Affiliated Hospital of Guangzhou Medical University)

  • Guang-Rong Yan

    (The Third Affiliated Hospital of Guangzhou Medical University)

Abstract

N6-methyladenosine (m6A) is the most prevalent modification in eukaryotic RNAs. The biological importance of m6A relies on m6A readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of m6A readers are involved in the m6A recognition on RNAs. Here we discover that the long noncoding RNA (lncRNA) LINC00266-1 encodes a 71-amino acid peptide. The peptide mainly interacts with the RNA-binding proteins, including the m6A reader IGF2BP1, and is thus named “RNA-binding regulatory peptide” (RBRP). RBRP binds to IGF2BP1 and strengthens m6A recognition by IGF2BP1 on RNAs, such as c-Myc mRNA, to increase the mRNA stability and expression of c-Myc, thereby promoting tumorigenesis. Cancer patients with RBRPhigh have a poor prognosis. Thus, the oncopeptide RBRP encoded by LINC00266-1 is a regulatory subunit of m6A readers and strengthens m6A recognition on the target RNAs by the m6A reader to exert its oncogenic functions.

Suggested Citation

  • Song Zhu & Ji-Zhong Wang & De Chen & Yu-Tian He & Nan Meng & Min Chen & Rui-Xun Lu & Xin-Hui Chen & Xiao-Lan Zhang & Guang-Rong Yan, 2020. "An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15403-9
    DOI: 10.1038/s41467-020-15403-9
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    Cited by:

    1. Xiao-Lan Zhang & Xin-Hui Chen & Binwu Xu & Min Chen & Song Zhu & Nan Meng & Ji-Zhong Wang & Huifang Zhu & De Chen & Jin-Bao Liu & Guang-Rong Yan, 2023. "K235 acetylation couples with PSPC1 to regulate the m6A demethylation activity of ALKBH5 and tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Xiang Zhang & Huilong Yin & Xiaofang Zhang & Xunliang Jiang & Yongkang Liu & Haolin Zhang & Yingran Peng & Da Li & Yanping Yu & Jinbao Zhang & Shuli Cheng & Angang Yang & Rui Zhang, 2022. "N6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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