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Lactylation-Dependent DDX18 Nucleolar Escape Regulates CD44 mRNA Stability to Drive Fibrotic Progression in Kidney Disease [RIP-Seq]

ABSTRACT: To investigate the function of K116 lactylation of DDX18, we performed RIP-seq analysis in DDX18-deficient HK-2 cells transfected with either DDX18-WT or the DDX18-K116R mutant plasmid to compare the RNA-binding profiles of DDX18-WT and DDX18-K116R.

ORGANISM(S): Homo sapiens

PROVIDER: GSE333824 | GEO | 2026/07/17

REPOSITORIES: GEO

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Lactylation-Dependent DDX18 Nucleolar Escape Regulates CD44 mRNA Stability to Drive Fibrotic Progression in Kidney Disease

Project description:To investigate the function of k116 lactylation of DDX18, we then performed gene expression profiling analysis using data obtained from RNA-seq of DDX18-deficient HK-2 cells transfected with DDX18-WT or the DDX18-K116R mutant plasmid.

2026-07-17 | GSE333635 | GEO

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DDX18 safeguards rDNA epigenetic landscape by counteracting PRC2 and maintains ESC identity

Project description:Here we have RNA binding protein DDX18 connecting rRNA transcription to early embryo development and embryonic stem cell (ESC) identity maintenance. DDX18 mutant embryos suffer lethality during preimplantation development. DDX18 depletion impairs ESC self-renewal and pluripotency, which phenotype-copies RNA polymerase I (RNAPI) inhibition. Mechanistically, DDX18 is recruited to rDNA by RNAPI transcription machinery and senses rRNA transcription by binding to pre-rRNA. In nucleolus, DDX18 surrounds DFC ring and interacts with PRC2. In the presence of transcribed pre-rRNA, DDX18 interaction with PRC2 makes EZH2 unstably binding to the other components of PRC2, thereby preventing PRC2 engagement and counteracting H3K27me3 mediated silencing at rDNA chromatin. Together, our study shows that DDX18 plays important roles in safeguarding ESCs identity through regulating epigenetic states of rDNA locus and maintaining euchromatin structure in nucleolus.

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Project description:This study explores the crucial role of the nucleolus-specific RNA helicase DDX18 in maintaining the pluripotency of human embryonic stem cells. We demonstrate that DDX18 coordinates nucleolus phase separation and chromatin organization by interacting with NPM1 in the granular component of the nucleolus, facilitated by nucleolar RNA species. The absence of DDX18 disrupts immiscible nucleolar substructures, significantly affecting centromere clustering and perinucleolar heterochromatin (PNH) formation.

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The influence of DDX18 high expression in PDAC cells Hs766T on the expression of other intracellular molecules

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Effects of DDX18 on chromatin characteristics

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