In this paper we study the error rate of RNA synthesis in the look-ahead model for the
random walk of RNA polymerase along DNA during transcription. The model’s central
assumption is the existence of a window of activity in which
ribonucleoside triphosphates (rNTPs) bind reversibly to the template DNA strand before
being hydrolyzed and linked covalently to the nascent RNA chain. An unknown, but
important, integer parameter of this model is the window size w. Here, we
use mathematical analysis and computer simulation to study the rate at which
transcriptional errors occur as a function of w. We find dramatic
reduction in the error rate of transcription as w increases, especially
for small values of w. The error reduction method provided by look-ahead
occurs before hydrolysis and covalent linkage of rNTP to the nascent RNA
chain, and is therefore distinct from error correction mechanisms that have previously
been considered.