Autor: |
Jason Saba, Xien Yu Chua, Tatiana V Mishanina, Dhananjaya Nayak, Tricia A Windgassen, Rachel Anne Mooney, Robert Landick |
Jazyk: |
angličtina |
Rok vydání: |
2019 |
Předmět: |
|
Zdroj: |
eLife, Vol 8 (2019) |
Druh dokumentu: |
article |
ISSN: |
2050-084X |
DOI: |
10.7554/eLife.40981 |
Popis: |
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 (i) is multipartite; (ii) 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 (iii) 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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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