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lncRNA-ZFAS1, an emerging gate-keeper in DNA damage-dependent transcriptional regulation [CDK9 ChIP-Seq]

GSE268444 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2024/06/02 Platform GPL24676
Summary
Numerous long noncoding RNAs (lncRNAs) are generated in response to external stimuli, but the scope and functions of such activity are not known. Here, we provide insight into how the transcription of lncRNAs are connected to DNA damage response by identifying a lncRNA ZFAS1, which is required for cell cycle arrest, transcription regulation and DNA repair. Mechanistically, ZFAS1 facilitates the changing hyperphosphorylated forms of the large subunit of RNAPII around transcription initiation sites by directly targeting the regulated genes. We revealed extensive transcription shutdown and concomitant stimulated engagement of RNAPII-Ser2P are crucial for repair and cell survival upon genotoxic stress. Finally, ZFAS1 knockout in mice dampened transcription-coupled nucleotide excision repair (TC-NER) and led to kidney dysplasia. Our study extends the understanding of lncRNAs in DNA damage repair (DDR) and implies a protective role of lncRNA against DDR-deficient developmental disorders.
Published in
IncRNA-ZFAS1, an Emerging Gate-Keeper in DNA Damage-Dependent Transcriptional Regulation
Liu J, Lu Q, Fan Z et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2025 · PMID 40411394 · doi:10.1002/advs.202412385
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Also filed as BioProject PRJNA1117388 and SRA study SRP510258. Searching any of these in the dataset finder brings you back here.

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