The elemental mechanism of transcriptional pausing [article]

Jason Saba, Xien Chua, Tatiana V Mishanina, Dhananjaya Nayak, Tricia A Windgassen, Rachel Anne Mooney, Robert Landick
2018 bioRxiv   pre-print
Transcriptional pausing underpins regulation of cellular RNA biogenesis. A consensus pause sequence that acts on RNA polymerases (RNAPs) from bacteria to mammals halts RNAP in an elemental paused state from which longer-lived pauses can arise. Although the structural foundations of pauses prolonged by backtracking or nascent RNA hairpins are recognized, the fundamental mechanism of the elemental pause is less well-defined. Here we report a mechanistic dissection that establishes the elemental
more » ... use signal (i) is multipartite; (ii) causes a modest conformational shift that puts RNAP in an off-pathway state in which template base loading but not RNA translocation is inhibited; and (iii) can easily enter pretranslocated and one-base-pair backtracked states despite principally occupying the half-translocated state observed in cryo-EM structures of paused RNAPs. Our findings provide a mechanistic basis for the elemental pause and a framework to understand how pausing is modulated by sequence, cellular conditions, and regulators.
doi:10.1101/422220 fatcat:4n74iivr5zaubbofoz54tj375m