Mechanisms of σ⁵⁴-Dependent Transcription Initiation and Regulation

Cellular RNA polymerase is a multi-subunit macromolecular assembly responsible for gene transcription, a highly regulated process conserved from bacteria to humans. In bacteria, sigma factors are employed to mediate gene-specific expression in response to a variety of environmental conditions. The major variant σ factor, σ⁵⁴, has a specific role in stress responses. Unlike σ⁷⁰-dependent transcription, which often can spontaneously proceed to initiation, σ⁵⁴-dependent transcription requires an additional ATPase protein for activation. As a result, structures of a number of distinct functional states during the dynamic process of transcription initiation have been captured using the σ⁵⁴ system with both x-ray crystallography and cryo electron microscopy, furthering our understanding of σ⁵⁴-dependent transcription initiation and DNA opening. Comparisons with σ⁷⁰ and eukaryotic polymerases reveal unique and common features during transcription initiation.