The Elemental Mechanism of Transcriptional Pausing

Overview

Journal Elife

Specialty Biology

Date 2019 Jan 9

PMID 30618376

Citations 38

Authors

Jason Saba

Xien Yu Chua

Tatiana V Mishanina

Dhananjaya Nayak

Tricia A Windgassen

Rachel Anne Mooney

Robert Landick

Affiliations

Soon will be listed here.

Abstract

Transcriptional pausing underlies 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 pause signal () is multipartite; () causes a modest conformational shift that puts γ-proteobacterial RNAP in an off-pathway state in which template base loading but not RNA translocation is inhibited; and () allows RNAP to enter pretranslocated and one-base-pair backtracked states easily even though the half-translocated state observed in paused cryo-EM structures rate-limits pause escape. 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.

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