Merging Established Mechanisms with New Insights: Condensates, Hubs, and the Regulation of RNA Polymerase II Transcription. Issue 1 (15th January 2022)

• Record Type: Journal Article
• Authors: Palacio, Megan; Taatjes, Dylan J.
• Is Part Of: Journal of molecular biology. Volume 434:Issue 1(2022)
• Publication Date: 2022-01-15
• Subjects: transcription -- condensates -- liquid-liquid phase separation -- mediator -- RNA polymerase II; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2021.167216
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: The precise role of condensates in regulation of human pol II transcription remains unclear. Conventional models share many features with condensate-dependent regulation. Condensates invoke new mechanisms for transcription regulation, and therapeutic strategies. Abstract: The regulation of RNA polymerase II (pol II) transcription requires a complex and context-specific array of proteins and protein complexes, as well as nucleic acids and metabolites. Every major physiological process requires coordinated transcription of specific sets of genes at the appropriate time, and a breakdown in this regulation is a hallmark of human disease. A proliferation of recent studies has revealed that many general transcription components, including sequence-specific, DNA-binding transcription factors, Mediator, and pol II itself, are capable of liquid–liquid phase separation, to form condensates that partition these factors away from the bulk aqueous phase. These findings hold great promise for next-level understanding of pol II transcription; however, many mechanistic aspects align with more conventional models, and whether phase separation per se regulates pol II activity in cells remains controversial. In this review, we describe the conventional and condensate-dependent models, and why their similarities and differences are important. We also compare and contrast these models in the context of genome organization and pol II transcription (initiation, elongation, and termination), and highlight the central role of RNA in these processes. Finally, we discuss mutations that disrupt normal partitioning of transcription factors, and how this may contribute to disease.