Nature Communications (Oct 2024)

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

  • Xiaoyu Zhang,
  • Tianyi Ding,
  • Fan Yang,
  • Jixing Zhang,
  • Haowen Xu,
  • Yiran Bai,
  • Yibing Shi,
  • Jiaqi Yang,
  • Chaoqun Chen,
  • Chengbo Zhu,
  • He Zhang

DOI
https://doi.org/10.1038/s41467-024-53493-x
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 20

Abstract

Read online

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.