Backtracking and Proofreading in DNA Transcription

Biological cell function crucially relies on the accuracy of RNA sequences, transcribed from the DNA genetic code. To ensure sufficiently high fidelity in the face of high spontaneous error rates during transcription, error correction mechanisms must play an important role. A particular mechanism of transcriptional error correction involves backtracking of the RNA polymerase and RNA cleavage. Motivated by recent single molecule experiments characterizing the dynamics of backtracking, we present a microscopic model of this editing process. We show that such a mechanism can yield error frequencies that are in agreement with in vivo observations.

Figure 1

(a) Schematic illustration of the model. The RNA is marked by $3^{\prime }$ and $5^{\prime }$. The transcription elongation complex (TEC) is depicted in the active ($n,m=0$) (top) and in a backtracked ($n,m=3$) (bottom) state, both with $M=5$. (b) Schematic illustration of the TEC dynamics at a given position $n$. The TEC will eventually polymerize forward or cleave from one of the backtracked states.

Figure 2

The error fraction as a function of $K$ ($M=1$ case). Analytic results [Eq. (3)] are plotted as solid lines, while markers show results obtained from stochastic simulations of the elongation model. Top: The error fraction for different positions with ${\alpha }_1={10}^{-4}$, ${\alpha }_2={10}^{-2}$, $ϵ={10}^{-2}$, and $N=9$. Bottom: The error fraction for different cleavage efficiencies with $ϵ={10}^{-2}$, $n=N-2$, and $N=4$. Dashed lines show limits discussed in text.

Figure 3

Error fraction as a function of $K$ ($M=2$ case). Results were obtained using stochastic simulations of the model for $N=4$, $ϵ={10}^{-2}$, and ${\alpha }_1={10}^{-2},{10}^{-4}$.