One of the fascinating features of biochemical processes is to optimize stationary flux by maintaining superior accuracy. The low error in biological systems is a consequence of their undergoing proofreading mechanisms. A small subunit of RNA polymerase II plays a vital role in increasing the efficiency of the transcription process with the help of multiple proofreading cycles. We developed a discrete-state stochastic framework to understand the transcription process of DNA-dependent RNA polymerase-II in eukaryotic organisms. Using the first-passage analysis, we investigate the trade-off between the characteristic properties such as error, speed, and energy dissipation cost. We also defined a metric to determine the relative importance of each typical property. The trade-off is observed between error rate and mean first-passage time for the variation of the polymerization rate constant. The results indicate that the RNAP II is optimized first for speed and has energy dissipation cost as the second priority, unlike the RdRp complex. Our theoretical findings provide a detailed picture of how the proofreading mechanisms increase the productivity of the RNAPII transcription process.

Trade-offs between flux, accuracy, and energy dissipation cost in RNA Polymerase-II transcription with proofreading

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ACS Fall 2022

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