Sandra J. Greive, Jim P. Goodarzi, Steven E.
Weitzel and Peter H. von Hippel
Transcript elongation by RNA polymerase involves the sequential
appearance of several alternative and off-pathway states of the transcript
elongation complex (TEC), and this complicates modeling of the kinetics of the
transcription elongation process. Based on solutions of the chemical master
equation for such transcription systems as a function of time, we here develop
a modular scheme for simulating such kinetic transcription data. This scheme
deals explicitly with the problem of TEC desynchronization as transcript
synthesis proceeds, and develops kinetic modules to permit the various
alternative states of the TECs (paused states, backtracked states, arrested
states, and terminated states) to be introduced one-by-one as needed. In this
way, we can set up a comprehensive kinetic model of appropriate complexity to
fit the known transcriptional properties of any given DNA template and set of
experimental conditions, including regulatory cofactors. In the companion
article, this modular scheme is successfully used to model kinetic
transcription elongation data obtained by bulk-gel electrophoresis quenching
procedures and real-time surface plasmon resonance methods from a template of
known sequence that contains defined pause, stall, and termination sites.
Journal: Biophysical Journal
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