{"title":"ZC3H4/Restrictor Exerts a Stranglehold on Pervasive Transcription.","authors":"Chris Estell, Steven West","doi":"10.1016/j.jmb.2024.168707","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168707"},"PeriodicalIF":4.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jmb.2024.168707","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Journal of Molecular Biology (JMB) provides high quality, comprehensive and broad coverage in all areas of molecular biology. The journal publishes original scientific research papers that provide mechanistic and functional insights and report a significant advance to the field. The journal encourages the submission of multidisciplinary studies that use complementary experimental and computational approaches to address challenging biological questions.
Research areas include but are not limited to: Biomolecular interactions, signaling networks, systems biology; Cell cycle, cell growth, cell differentiation; Cell death, autophagy; Cell signaling and regulation; Chemical biology; Computational biology, in combination with experimental studies; DNA replication, repair, and recombination; Development, regenerative biology, mechanistic and functional studies of stem cells; Epigenetics, chromatin structure and function; Gene expression; Membrane processes, cell surface proteins and cell-cell interactions; Methodological advances, both experimental and theoretical, including databases; Microbiology, virology, and interactions with the host or environment; Microbiota mechanistic and functional studies; Nuclear organization; Post-translational modifications, proteomics; Processing and function of biologically important macromolecules and complexes; Molecular basis of disease; RNA processing, structure and functions of non-coding RNAs, transcription; Sorting, spatiotemporal organization, trafficking; Structural biology; Synthetic biology; Translation, protein folding, chaperones, protein degradation and quality control.