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 and He Zhang ()
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Xiaoyu Zhang: Tongji University
Tianyi Ding: Tongji University
Fan Yang: Tongji University
Jixing Zhang: Tongji University
Haowen Xu: Tongji University
Yiran Bai: Tongji University
Yibing Shi: Tongji University
Jiaqi Yang: Tongji University
Chaoqun Chen: Tongji University
Chengbo Zhu: Tongji University
He Zhang: Tongji University

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53493-x

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