Accurate transcription is required for the faithful expression of genetic information. However, relatively little is known about the molecular mechanisms that control the fidelity of transcription, or the conservation of these mechanisms across the tree of life. To address these issues, we measured the error rate of transcription in five organisms of increasing complexity and found that the error rate of RNA polymerase II ranges from 2.9 × 10^-6 ± 1.9 × 10^-7/bp in yeast to 4.0 × 10^-6 ± 5.2 × 10^-7/bp in worms, 5.69 × 10^-6 ± 8.2 × 10^-7/bp in flies, 4.9 × 10^-6 ± 3.6 × 10^-7/bp in mouse cells and 4.7 × 10^-6 ± 9.9 × 10^-8/bp in human cells. These error rates were modified by various factors including aging, mutagen treatment and gene modifications. For example, the deletion or modification of several related genes increased the error rate substantially in both yeast and human cells. This research highlights the evolutionary conservation of factors that control the fidelity of transcription. Additionally, these experiments provide a reasonable estimate of the error rate of transcription in human cells and identify disease alleles in a subunit of RNA polymerase II that display error-prone transcription. Finally, we provide evidence suggesting that the error rate and spectrum of transcription co-evolved with our genetic code.

• PMID: 36941254
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Journal Article | Research Support, N.I.H., Extramural

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Chung C, Verheijen BM, Navapanich Z, McGann EG, Shemtov S, Lai GJ, Arora P, Towheed A, Haroon S, Holczbauer A, ... Show all

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