ArticleNature communications2016
Bridge helix bending promotes RNA polymerase II backtracking through a critical and conserved threonine residue.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
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- Automated Path Searching Reveals the Mechanism of Hydrolysis Enhancement by T4 Lysozyme Mutants.International journal of molecular sciences · 2022Article
- Structural insights into the dual activities of the two-barrel RNA polymerase QDE-1.Nucleic acids research · 2022Article
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Authors and funding
8 authors.
Funding
Abstract
The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH residue T831 as a sensing probe for the 3'-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3'-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation.
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