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J. Chem. Phys. 135, 245101 (2011); http://dx.doi.org/10.1063/1.3671644 (10 pages)

Cotranscriptional folding kinetics of ribonucleic acid secondary structures

Peinan Zhao1, Wenbing Zhang1, and Shi-Jie Chen2

1Department of Physics, Wuhan University, Wuhan 430072, People's Republic of China
2Department of Physics and Astronomy and Department of Biochemistry University of Missouri, Columbia, Missouri 65211, USA

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(Received 12 August 2011; accepted 2 December 2011; published online 22 December 2011)

We develop a systematic helix-based computational method to predict RNA folding kinetics during transcription. In our method, the transcription is modeled as stepwise process, where each step is the transcription of a nucleotide. For each step, the kinetics algorithm predicts the population kinetics, transition pathways, folding intermediates, and the transcriptional folding products. The folding pathways, rate constants, and the conformational populations for cotranscription folding show contrastingly different features than the refolding kinetics for a fully transcribed chain. The competition between the transcription speed and rate constants for the transitions between the different nascent structures determines the RNA folding pathway and the end product of folding. For example, fast transcription favors the formation of branch-like structures than rod-like structures and chain elongation in the folding process may reduce the probability of the formation of misfolded structures. Furthermore, good theory-experiment agreements suggest that our method may provide a reliable tool for quantitative prediction for cotranscriptional RNA folding, including the kinetics for the population distribution for the whole conformational ensemble.

© 2011 American Institute of Physics

Article Outline

  1. INTRODUCTION
  2. THEORY AND METHOD
    1. Master equation
    2. Helices as building blocks
    3. Formation and disruption of a helix
    4. Exchange between two helices
    5. Predicting cotranscriptional folding
  3. RESULTS
    1. Competition of the different rate processes determines the cotranscriptional folding pathway
    2. Transcription speed affects the end product of transcription
    3. Transcription direction affects the folding pathway and folding products
  4. DISCUSSION

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0021-9606 (print)  
1089-7690 (online)

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