ArticleScience advances2025
ZC3H4 safeguards genome integrity by preventing transcription-replication conflicts at noncoding RNA loci.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
5 citing papers in PubMed.
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Polymerase face-off: emerging concepts in transcription-replication coordination.EMBO reports · 2026Review
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Identification and Expression Analysis of CCCH Zinc Finger Proteins in Mulberry (International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The cellular networks that maintain genome stability encompass numerous pathways involved in all aspects of nucleic acid metabolism. Through bioinformatic analysis, we identified the Zinc Finger CCCH-Type Containing 4 protein (ZC3H4), a suppressor of noncoding RNA (ncRNA) production, as a pivotal player in this system. Experimentally, ZC3H4 deficiency led to increased DNA damage, abnormal mitosis, and cellular senescence. Biochemical analysis and super-resolution microscopy revealed that the loss of ZC3H4 increased replication stress (RS)-a major driver of genome instability-by inducing a hypertranscription state that promoted R loop formation and transcription-replication conflicts (TRCs), both of which drive RS. Further bioinformatic analysis demonstrated that ZC3H4 preferentially binds to genomic regions prone to TRCs and R loops, where it suppresses ncRNA bursts, functioning as part of the Restrictor complex. Our findings identify ZC3H4 as a crucial factor in maintaining genome integrity, strategically positioned at the critical intersection of DNA and RNA synthesis.
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Registered trials
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