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Peptidylprolyl isomerase A guides SENP5/GAU1 DNA-lncRNA triplex generation for driving tumorigenesis

Author

Listed:
  • Xiaoyu Zhang

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Tianyi Ding

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Fan Yang

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Jixing Zhang

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Haowen Xu

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Yiran Bai

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Yibing Shi

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Jiaqi Yang

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Chaoqun Chen

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • Chengbo Zhu

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

  • He Zhang

    (Tongji University
    Medical Department of Jinggangshan University
    Jinggangshan University)

Abstract

The three-stranded DNA-RNA triplex hybridization is involved in various biological processes, including gene expression regulation, DNA repair, and chromosomal stability. However, the DNA-RNA triplex mediating mechanisms underlying tumorigenesis remain to be fully elucidated. Here, we show that peptidylprolyl isomerase A (PPIA) serves as anchor to recruit GAU1 lncRNA by interacting with exon 4 of GAU1 and enhances the formation of SENP5/GAU1 DNA-lncRNA triplex. Intriguingly, TFR4 region of GAU1 exon 3 and TTS4 region of SENP5 promoter DNA constitute fragments forming the SENP5/GAU1 triplex. The SENP5/GAU1 triplex subsequently triggers the recruitment of the methyltransferase SET1A to exon 1 of GAU1, leading to the enrichment of H3K4 trimethylation and the activation of SENP5 transcription for driving the tumorigenesis of gastric cancer in vitro and in vivo. Our study reveals a mechanism of PPIA-guided SENP5/GAU1 DNA-lncRNA triplex formation in tumorigenesis and providing a concept in the dynamics of isomerase assisted DNA-RNA hybridization.

Suggested Citation

  • Xiaoyu Zhang & Tianyi Ding & Fan Yang & Jixing Zhang & Haowen Xu & Yiran Bai & Yibing Shi & Jiaqi Yang & Chaoqun Chen & Chengbo Zhu & He Zhang, 2024. "Peptidylprolyl isomerase A guides SENP5/GAU1 DNA-lncRNA triplex generation for driving tumorigenesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53493-x
    DOI: 10.1038/s41467-024-53493-x
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    1. Yu Xu & James McSally & Ioan Andricioaei & Hashim M. Al-Hashimi, 2018. "Modulation of Hoogsteen dynamics on DNA recognition," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Igor Martianov & Aroul Ramadass & Ana Serra Barros & Natalie Chow & Alexandre Akoulitchev, 2007. "Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript," Nature, Nature, vol. 445(7128), pages 666-670, February.
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