ZC3H4/Restrictor Exerts a Stranglehold on Pervasive Transcription

• Published in: Journal of molecular biology 2025-01, Vol.437 (1), p.168707, Article 168707
• Main Authors: Estell, Chris, West, Steven
• Format: Article
• Language: English
• Subjects: DNA-directed RNA polymerase; Exosome Multienzyme Ribonuclease Complex; exosomes; Gene Expression Regulation; Humans; molecular biology; non-coding RNA; PNUTS; restrictor; RNA; RNA polymerase II; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; transcription termination; Transcription, Genetic; ZC3H4
• ISSN: 0022-2836; 1089-8638; 1089-8638
• DOI: 10.1016/j.jmb.2024.168707

[Display omitted] •The Restrictor complex restrains unproductive/pervasive transcription.•Restrictor contains ZC3H4, WDR82, ARS2 and Casein Kinase 2.•Restrictor acts in proximity to other transcriptional termination pathways.•Restrictor has similarities to other transcriptional termination mechanisms. The regulation of transcription by RNA polymerase II (RNAPII) underpins all cellular processes and is perturbed in thousands of diseases. In humans, RNAPII transcribes ∼20000 protein-coding genes and engages in apparently futile non-coding transcription at thousands of other sites. Despite being so ubiquitous, this transcription is usually attenuated soon after initiation and the resulting products are immediately degraded by the nuclear exosome. We and others have recently described a new complex, “Restrictor”, which appears to control such unproductive transcription. Underpinned by the RNA binding protein, ZC3H4, Restrictor curtails unproductive/pervasive transcription genome-wide. Here, we discuss these recent discoveries and speculate on some of the many unknowns regarding Restrictor function and mechanism.