Evolutionary conservation of the fidelity of transcription

Claire Chung, Bert M. Verheijen, Zoe Navapanich, Eric G. McGann, Sarah Shemtov, Guan-Ju Lai, Payal Arora, Atif Towheed, Suraiya Haroon, Agnes Holczbauer, Sharon Chang, Zarko Manojlovic, Stephen Simpson, Kelley W. Thomas, Craig Kaplan, Peter Hasselt, Marc Timmers, Dorothy Erie, Lin Chen, Jean-Franćois Gout and Marc Vermulst ()
Additional contact information
Claire Chung: University of Southern California
Bert M. Verheijen: University of Southern California
Zoe Navapanich: University of Southern California
Eric G. McGann: University of Southern California
Sarah Shemtov: University of Southern California
Guan-Ju Lai: University of Southern California
Payal Arora: University of Pittsburgh
Atif Towheed: Center for Mitochondrial and Epigenomic Medicine
Suraiya Haroon: Center for Mitochondrial and Epigenomic Medicine
Agnes Holczbauer: Center for Mitochondrial and Epigenomic Medicine
Sharon Chang: University of Southern California
Zarko Manojlovic: University of Southern California
Stephen Simpson: University of New Hampshire
Kelley W. Thomas: University of New Hampshire
Craig Kaplan: University of Pittsburgh
Peter Hasselt: University of Utrecht
Marc Timmers: Medical Center - University of Freiburg
Dorothy Erie: University of North Carolina
Lin Chen: University of Southern California
Jean-Franćois Gout: Mississippi State University
Marc Vermulst: University of Southern California

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-36525-w

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