RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits
Abstract
Errors during transcription may play an important role in determining cellular phenotypes: the RNA polymerase error rate is >4 orders of magnitude higher than that of DNA polymerase and errors are amplified >1000-fold due to translation. However, current methods to measure RNA polymerase fidelity are low-throughout, technically challenging, and organism specific. Here I show that changes in RNA polymerase fidelity can be measured using standard RNA sequencing protocols. I find that RNA polymerase is error-prone, and these errors can result in splicing defects. Furthermore, I find that differential expression of RNA polymerase subunits causes changes in RNA polymerase fidelity, and that coding sequences may have evolved to minimize the effect of these errors. These results suggest that errors caused by RNA polymerase may be a major source of stochastic variability at the level of single cells.
Article and author information
Author details
Reviewing Editor
- Patrick Cramer, Max Planck Institute for Biophysical Chemistry, Germany
Publication history
- Received: July 8, 2015
- Accepted: October 26, 2015
- Accepted Manuscript published: December 10, 2015 (version 1)
- Version of Record published: December 29, 2015 (version 2)
Copyright
© 2015, Carey
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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