Three states of HelD color-coded according to the domain structure
RNA synthesis is central to life, and RNA polymerase (RNAP) depends on accessory factors for recovery from stalled states and adaptation to environmental changes. Here, T. Kouba, J. Dohnálek, L. Krásný et.al.investigated the mechanism by which a helicase-like factor HelD recycles RNAP. They report a cryo-EM structure of a complex between the Mycobacterium smegmatis RNAP and HelD. The crescent-shaped HelD simultaneously penetrates deep into two RNAP channels that are responsible for nucleic acids binding and substrate delivery to the active site, thereby locking RNAP in an inactive state. They show that HelD prevents non-specific interactions between RNAP and DNA and dissociates stalled transcription elongation complexes. The liberated RNAP can either stay dormant, sequestered by HelD, or upon HelD release, restart transcription. Their results provide insights into the architecture and regulation of the highly medically-relevant mycobacterial transcription machinery and define HelD as a clearing factor that releases RNAP from nonfunctional complexes with nucleic acids.
Kouba, T.; Koval’, T.; Sudzinová, P.; Pospíšil, J.; Brezovská, B.; Hnilicová, J.; Šanderová, H.; Janoušková, M.; Šiková, M.; Halada, P.; Sýkora, M.; Barvík, I.; Nováček, J.; Trundová, M.; Dušková, J.; Skálová, T.; URee Chon; Murakami, K. S.; Dohnálek, J. & Krásný, L.: Mycobacterial HelD is a nucleic acids-clearing factor for RNA polymerase, Nature Comm. (2020) 11, 6419, https://doi.org/10.1038/s41467-020-20158-4