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- W4319936698 abstract "During transcriptional elongation, RNA polymerase (RNAP) occasionally pauses following the incorporation of a wrong (non-complementary) nucleotide. Cleavage of dinucleotides after the pauses serves as a proofreading mechanism that increases transcriptional accuracy. In vivo, the accuracy is further improved by cleavage factors such as TFIIS that bind to RNAP. However, it is not fully clear why RNAPs pause and why cleavage-factor assisted proofreading is necessary since transcriptional errors in vitro are of the same order as those in downstream translation. Here, we developed a chemical-kinetic model for transcription that allowed us to investigate the role of pauses, dinucleotide cleavages, and accessory proteins on RNAP speed and accuracy. We found that irrespective of the presence of cleavage factors, the polymerization rate is set by the speed-accuracy trade-off. In contrast, no trade-off exists for the rate of cleavage as the proofreading increases both speed and accuracy. The results further demonstrate that the existence of long pauses is essential for high accuracy whereas the cleavage-factor stimulated proofreading in the presence of pausing optimizes the speed of transcription. Our theoretical method and results provide a microscopic picture of how the synergy between pausing and cleavage activity in the presence of polymerase-binding proteins regulates transcription elongation." @default.
- W4319936698 created "2023-02-11" @default.
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- W4319936698 date "2023-02-01" @default.
- W4319936698 modified "2023-09-25" @default.
- W4319936698 title "Synergy between pausing and cleavage-factor-assisted-proofreading results in optimal transcription speed and tolerable accuracy" @default.
- W4319936698 doi "https://doi.org/10.1016/j.bpj.2022.11.579" @default.
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