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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Detalles Bibliográficos
Autor: Carey, Lucas, 1980-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/25767
Acceso en línea:http://hdl.handle.net/10230/25767
http://dx.doi.org/10.7554/eLife.09945
Access Level:acceso abierto
Palabra clave:RNA-polimerases
RNA polymerase
RNA-seq
S. cerevisiae
Biological errors
Computational biology
Evolutionary biology
Genomics
Human
Splicing
Systems biology
Descripción
Sumario: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.