RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits

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 polymera...

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Bibliographic Details
Author: Carey, Lucas, 1980-
Format: article
Status:Published version
Publication Date:2015
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/25767
Online Access:http://hdl.handle.net/10230/25767
http://dx.doi.org/10.7554/eLife.09945
Access Level:Open access
Keyword:RNA-polimerases
RNA polymerase
RNA-seq
S. cerevisiae
Biological errors
Computational biology
Evolutionary biology
Genomics
Human
Splicing
Systems biology
Description
Summary: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.