Thermodynamic and kinetic modeling of transcriptional pausing

Vasisht R. Tadigotla, Dáibhid Ó Maoiléidigh, Anirvan Sengupta, Vitaly Epshtein, Richard Ebright, Evgeny Nudler, Andrei E. Ruckenstein

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

We present a statistical mechanics approach for the prediction of backtracked pauses in bacterial transcription elongation derived from structural models of the transcription elongation complex (EC). Our algorithm is based on the thermodynamic stability of the EC along the DMA template calculated from the sequence-dependent free energy of DNA-DNA, DNA-RNA, and RNA-RNA base pairing associated with (i) the translocational and size fluctuations of the transcription bubble; (ii) changes in the associated DNA-RNA hybrid; and (iii) changes in the cotranscriptional RNA secondary structure upstream of the RNA exit channel. The calculations involve no adjustable parameters except for a cutoff used to discriminate paused from nonpaused complexes. When applied to 100 experimental pauses in transcription elongation by Escherichia coli RNA polymerase on 10 DNA templates, the approach produces statistically significant results. We also present a kinetic model for the rate of recovery of backtracked paused complexes. A crucial ingredient of our model is the incorporation of kinetic barriers to backtracking resulting from steric clashes of EC with the cotranscriptionally generated RNA secondary structure, an aspect not included explicitly in previous attempts at modeling the transcription elongation process.

Original languageEnglish (US)
Pages (from-to)4439-4444
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number12
DOIs
StatePublished - Mar 21 2006

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Cotranscriptional folding
  • Statistical mechanics

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