Published online by Cambridge University Press: 28 April 2010
In this paper we study the error rate of RNA synthesis in the look-ahead model for therandom walk of RNA polymerase along DNA during transcription. The model’s centralassumption is the existence of a window of activity in whichribonucleoside triphosphates (rNTPs) bind reversibly to the template DNA strand beforebeing hydrolyzed and linked covalently to the nascent RNA chain. An unknown, butimportant, integer parameter of this model is the window size w. Here, weuse mathematical analysis and computer simulation to study the rate at whichtranscriptional errors occur as a function of w. We find dramaticreduction in the error rate of transcription as w increases, especiallyfor small values of w. The error reduction method provided by look-aheadoccurs before hydrolysis and covalent linkage of rNTP to the nascent RNAchain, and is therefore distinct from error correction mechanisms that have previouslybeen considered.