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.

authors

Silva DA,Weiss DR,Pardo Avila F,Da LT,Levitt M,Wang D,Huang X

doi

10.1073/pnas.1315751111

subject

Has Abstract

pub_date

2014-05-27 00:00:00

pages

7665-70

issue

21

eissn

0027-8424

issn

1091-6490

pii

1315751111

journal_volume

111

pub_type

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