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Peptidylprolyl isomerase A guides SENP5/GAU1 DNA-lncRNA triplex generation for driving tumorigenesis
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Peptidylprolyl isomerase A guides SENP5/GAU1 DNA-lncRNA triplex generation for driving tumorigenesis
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Journal Article
Peptidylprolyl isomerase A guides SENP5/GAU1 DNA-lncRNA triplex generation for driving tumorigenesis
2024
Overview
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.
This study investigates the regulatory mechanisms of DNA-lncRNA triplexes, specifically their role in gastric cancer through the stable formation and precise oncogenic activity of the
SENP5/GAU1
triplex. It shows how PPIA orchestrates the
SENP5/GAU1
DNA-lncRNA triplex.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/89
/ 14
/ 38
/ 38/39
/ 38/77
/ 38/90
/ 45
/ 45/15
/ 45/29
/ Animals
/ Cancer
/ DNA
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Promoter Regions, Genetic - genetics
/ Regulatory mechanisms (biology)
/ RNA
/ RNA, Long Noncoding - genetics
/ RNA, Long Noncoding - metabolism
/ Science
/ Stomach Neoplasms - genetics
