Nanoscale organisation of transcription regulated by Myosin VI

While it is widely accepted there is temporal regulation of gene expression, more recently there has been an increase in studies of spatial regulation. Indeed, transcription can be observed within discrete foci throughout the nucleus with RNA Polymerase II (RNAPII) arranged in hubs or factories. The hubs bring together several genes and arrange the chromatin to enable simultaneous gene expression. The hubs are estimated to contain 4-30 RNAPII molecules in a region of 40-200 nm. Despite this quantitative knowledge, the mechanism of hub assembly, organisation and stability remains unknown. To this end, we have used advanced single molecule techniques to visualise RNAPII hubs and track their dynamics in live cells. Following our previous work on nuclear myosin VI, we know myosin-actin interactions are critical for RNAPII transcription, yet their function is unknown. Using a combination of super resolution imaging and 3D single molecule tracking we observed a loss of RNAPII organisation when myosin VI was knocked-down or inhibited. Lastly, we show how myosin VI uses a load-induced anchoring ability to stabilise RNAPII within the hubs. In this manner, myosin VI uses its force-sensing properties to regulate gene expression by organising the transcription centres.