The Influence of Look-Ahead on the Error Rate of Transcription

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.