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Millisecond dynamics of RNA polymerase II translocation at atomic resolution.


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.

SUBMITTER: Silva DA 

PROVIDER: S-EPMC4040580 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Millisecond dynamics of RNA polymerase II translocation at atomic resolution.

Silva Daniel-Adriano DA   Weiss Dahlia R DR   Pardo Avila Fátima F   Da Lin-Tai LT   Levitt Michael M   Wang Dong D   Huang Xuhui X  

Proceedings of the National Academy of Sciences of the United States of America 20140421 21


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 techniq  ...[more]

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