Myosin VI regulates the spatial organisation of mammalian transcription initiation

• Published in: Nature communications Vol. 13; no. 1; p. 1346
• Main Authors: Hari-Gupta, Yukti, Fili, Natalia, dos Santos, Ália, Cook, Alexander W., Gough, Rosemarie E., Reed, Hannah C. W., Wang, Lin, Aaron, Jesse, Venit, Tomas, Wait, Eric, Grosse-Berkenbusch, Andreas, Gebhardt, J. Christof M., Percipalle, Piergiorgio, Chew, Teng-Leong, Martin-Fernandez, Marisa, Toseland, Christopher P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-03-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/63; 38/15; 38/88; 631/1647/245; 631/45/147; 631/57/2282; 631/80/2373/2238; 631/80/386; Actin; Animals; Cell Nucleus - genetics; Cell Nucleus - metabolism; Chromatin; Clusters; DNA-directed RNA polymerase; Gene expression; Humanities and Social Sciences; Mammalian cells; Mammals; Mammals - genetics; Molecular motors; multidisciplinary; Myosin; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; Nuclei (cytology); Perturbation; Ribonucleic acid; RNA; RNA polymerase; RNA polymerase II; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Science; Science (multidisciplinary); Transcription initiation; Transcription, Genetic
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28962-w

During transcription, RNA Polymerase II (RNAPII) is spatially organised within the nucleus into clusters that correlate with transcription activity. While this is a hallmark of genome regulation in mammalian cells, the mechanisms concerning the assembly, organisation and stability remain unknown. Here, we have used combination of single molecule imaging and genomic approaches to explore the role of nuclear myosin VI (MVI) in the nanoscale organisation of RNAPII. We reveal that MVI in the nucleus acts as the molecular anchor that holds RNAPII in high density clusters. Perturbation of MVI leads to the disruption of RNAPII localisation, chromatin organisation and subsequently a decrease in gene expression. Overall, we uncover the fundamental role of MVI in the spatial regulation of gene expression.
The actin-based molecular motors, myosins, have also been linked to transcription, but their precise role has remained elusive. Here the authors show RNA polymerase II (RNAPII) is lost from chromatin upon myosin perturbation and that myosin acts as a molecular anchor to maintain RNAPII spatial organisation.