A Holistic View of Gene Expression in Archaea

Archaea represent an understudied yet abundant and important group of prokaryotic organisms. Their gene expression machinery is a streamlined version of pol II, including RNA polymerase and initiation, elongation and termination factors, which provide insights into the origin and evolution of transcription in eukaryotes. However, archaea have no nucleus and transcription and translation are coupled (‘TTC’). We aim to follow the two molecular machines that carry out each process, RNA polymerase and ribosome, by genome-scale profiling in vivo, and explore their structure and mechanisms in vitro. Key research questions include: • What is the structural and mechanistic basis of elongation and premature termination? • What is the role of PTMs during transcription elongation? • How can elongation factors facilitate transcription through Sulfolobus chromatin? • How do global RNAP- and ribosome profiles change to environmental cues? • How are proteomes and transcriptomes coordinated? • How do RNAPs ‘sense’ downstream events like the metabolic state of the cell? • What is the role of Spt4/5 and NusA1/2 in TTC? • How do cleavage factors and TTC collaborate during elongation? • What is the structural basis of TTC RNAP-ribosome complexes?