ArticleNucleic acids research2014
Trigger-helix folding pathway and SI3 mediate catalysis and hairpin-stabilized pausing by Escherichia coli RNA polymerase.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed.
- RNA polymerase inhibitors reveal active-site motions essential for the nucleotide addition cycle.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ppGpp regulates transcription elongation via direct and indirect inputs to RNA polymerase pausing and nucleotide addition.bioRxiv : the preprint server for biology · 2026Article
- RNA polymerase inhibitors reveal active-site motions essential for the nucleotide-addition cycle.bioRxiv : the preprint server for biology · 2026Article
- Heterogeneous template-dependent transcription dynamics of T7 RNAP revealed by single-molecule imaging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Widespread epistasis shapes RNA polymerase II active site function and evolution.Nature communications · 2025Article
- Targeting Bacterial RNA Polymerase: Harnessing Simulations and Machine Learning to Design Inhibitors for Drug-Resistant Pathogens.Biochemistry · 2025Review
- Bacteroides expand the functional versatility of a conserved transcription factor and transcribed DNA to program capsule diversity.Nature communications · 2024Article
- Architecture of the spinach plastid-encoded RNA polymerase.Nature communications · 2024Article
- Article
- Higher-order epistasis within Pol II trigger loop haplotypes.bioRxiv : the preprint server for biology · 2024Article
- Nanopore tweezers show fractional-nucleotide translocation in sequence-dependent pausing by RNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- RNA polymerase SI3 domain modulates global transcriptional pausing and pause-site fluctuations.Nucleic acids research · 2024Article
- An SI3-σ arch stabilizes cyanobacteria transcription initiation complex.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- An ensemble of interconverting conformations of the elemental paused transcription complex creates regulatory options.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Allosteric mechanism of transcription inhibition by NusG-dependent pausing of RNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Conserved Trigger Loop Histidine of RNA Polymerase II Functions as a Positional Catalyst Primarily through Steric Effects.Biochemistry · 2021Article
- Obligate movements of an active site-linked surface domain control RNA polymerase elongation and pausing via a Phe pocket anchor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Basic mechanisms and kinetics of pause-interspersed transcript elongation.Nucleic acids research · 2021Review
- Unboxing the T-box riboswitches-A glimpse into multivalent and multimodal RNA-RNA interactions.Wiley interdisciplinary reviews. RNA · 2020Review
- Role of the trigger loop in translesion RNA synthesis by bacterial RNA polymerase.The Journal of biological chemistry · 2020Article
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6 authors.
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Abstract
The conformational dynamics of the polymorphous trigger loop (TL) in RNA polymerase (RNAP) underlie multiple steps in the nucleotide addition cycle and diverse regulatory mechanisms. These mechanisms include nascent RNA hairpin-stabilized pausing, which inhibits TL folding into the trigger helices (TH) required for rapid nucleotide addition. The nascent RNA pause hairpin forms in the RNA exit channel and promotes opening of the RNAP clamp domain, which in turn stabilizes a partially folded, paused TL conformation that disfavors TH formation. We report that inhibiting TH unfolding with a disulfide crosslink slowed multiround nucleotide addition only modestly but eliminated hairpin-stabilized pausing. Conversely, a substitution that disrupts the TH folding pathway and uncouples establishment of key TH-NTP contacts from complete TH formation and clamp movement allowed rapid catalysis and eliminated hairpin-stabilized pausing. We also report that the active-site distal arm of the TH aids TL folding, but that a 188-aa insertion in the Escherichia coli TL (sequence insertion 3; SI3) disfavors TH formation and stimulates pausing. The effect of SI3 depends on the jaw domain, but not on downstream duplex DNA. Our results support the view that both SI3 and the pause hairpin modulate TL folding in a constrained pathway of intermediate states.
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