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.
journal_name
Proc Natl Acad Sci U S Aauthors
Silva DA,Weiss DR,Pardo Avila F,Da LT,Levitt M,Wang D,Huang Xdoi
10.1073/pnas.1315751111subject
Has Abstractpub_date
2014-05-27 00:00:00pages
7665-70issue
21eissn
0027-8424issn
1091-6490pii
1315751111journal_volume
111pub_type
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