title: Intermittent transcription dynamics for the rapid production of long transcripts of high fidelity.
abstract: Normal cellular function relies on the efficient and accurate readout of the genetic code. Single-molecule experiments show that transcription and replication are highly intermittent processes that are frequently interrupted by polymerases pausing and reversing directions. Although intermittent dynamics in replication are known to result from proofreading, their origin and significance during transcription remain controversial. Here, we theoretically investigate transcriptional fidelity and show that the kinetic scheme provided by the RNA-polymerase backtracking and transcript-cleavage pathway can account for measured error rates. Importantly, we find that intermittent dynamics provide an enormous increase in the rate of producing long transcripts of high fidelity. Our results imply that intermittent dynamics during transcription may have evolved as a way to mitigate the competing demands of speed and fidelity in the transcription of extended sequences.
authors.affiliation: Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, the Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Depken
authors.forename: Juan M R
authors.initials: JM
authors.lastname: Parrondo
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Grill
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D012313:RNA / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D012313:RNA; D012321:DNA-Directed RNA Polymerases