Recent advances in understanding RNA polymerase II structure and function

More than 50 years after the identification of RNA polymerase II, the enzyme responsible for the transcription of most eukaryotic genes, studies have continued to reveal fresh aspects of its structure and regulation. New technologies, coupled with years of development of a vast catalog of RNA polymerase II accessory proteins and activities, have led to new revelations about the transcription process. The maturation of cryo-electron microscopy as a tool for unraveling the detailed structure of large molecular machines has provided numerous structures of the enzyme and its accessory factors. Advances in biophysical methods have enabled the observation of a single polymerase’s behavior, distinct from work on aggregate population averages. Other recent work has revealed new properties and activities of the general initiation factors that RNA polymerase II employs to accurately initiate transcription, as well as chromatin proteins that control RNA polymerase II’s firing frequency, and elongation factors that facilitate the enzyme’s departure from the promoter and which control sequential steps and obstacles that must be navigated by elongating RNA polymerase II. There has also been a growing appreciation of the physical properties conferred upon many of these proteins by regions of each polypeptide that are of low primary sequence complexity and that are often intrinsically disordered. This peculiar feature of a surprisingly large number of proteins enables a disordered region of the protein to morph into a stable structure and creates an opportunity for pathway participants to dynamically partition into subcompartments of the nucleus. These subcompartments host designated portions of the chemical reactions that lead to mRNA synthesis. This article highlights a selection of recent findings that reveal some of the resolved workings of RNA polymerase II and its ensemble of supporting factors.