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Proc Natl Acad Sci U S A. 2014 May 27;111(21):7665-70. doi: 10.1073/pnas.1315751111. Epub 2014 Apr 21.

Millisecond dynamics of RNA polymerase II translocation at atomic resolution.

Author information

1
Department of Chemistry, The Hong Kong University of Science and Technology, Kowloon, Hong Kong;
2
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;
3
Department of Structural Biology, Stanford University, Stanford, CA 94085; and.
4
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 xuhuihuang@ust.hk dongwang@ucsd.edu.
5
Department of Chemistry, The Hong Kong University of Science and Technology, Kowloon, Hong Kong; xuhuihuang@ust.hk dongwang@ucsd.edu.

Abstract

Transcription is a central step in gene expression, in which the DNA template is processively read by RNA polymerase II (Pol II), synthesizing a complementary messenger RNA transcript. At each cycle, Pol II moves exactly one register along the DNA, a process known as translocation. Although X-ray crystal structures have greatly enhanced our understanding of the transcription process, the underlying molecular mechanisms of translocation remain unclear. Here we use sophisticated simulation techniques to observe Pol II translocation on a millisecond timescale and at atomistic resolution. We observe multiple cycles of forward and backward translocation and identify two previously unidentified intermediate states. We show that the bridge helix (BH) plays a key role accelerating the translocation of both the RNA:DNA hybrid and transition nucleotide by directly interacting with them. The conserved BH residues, Thr831 and Tyr836, mediate these interactions. To date, this study delivers the most detailed picture of the mechanism of Pol II translocation at atomic level.

KEYWORDS:

Markov state model; molecular dynamics; trigger loop

Comment in

PMID:
24753580
PMCID:
PMC4040580
DOI:
10.1073/pnas.1315751111
[Indexed for MEDLINE]
Free PMC Article
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