title: Reinitiated viral RNA-dependent RNA polymerase resumes replication at a reduced rate.
abstract: RNA-dependent RNA polymerases (RdRP) form an important class of enzymes that is responsible for genome replication and transcription in RNA viruses and involved in the regulation of RNA interference in plants and fungi. The RdRP kinetics have been extensively studied, but pausing, an important regulatory mechanism for RNA polymerases that has also been implicated in RNA recombination, has not been considered. Here, we report that RdRP experience a dramatic, long-lived decrease in its elongation rate when it is reinitiated following stalling. The rate decrease has an intriguingly weak temperature dependence, is independent of both the nucleotide concentration during stalling and the length of the RNA transcribed prior to stalling; however it is sensitive to RNA structure. This allows us to delineate the potential factors underlying this irreversible conversion of the elongation complex to a less active mode.
authors.affiliation: Faculty of Applied Sciences, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.
authors.forename: Igor D
authors.initials: ID
authors.lastname: Vilfan
authors.forename: Andrea
authors.initials: A
authors.lastname: Candelli
authors.forename: Susanne
authors.initials: S
authors.lastname: Hage
authors.forename: Antti P
authors.initials: AP
authors.lastname: Aalto
authors.forename: Minna M
authors.initials: MM
authors.lastname: Poranen
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Bamford
authors.forename: Nynke H
authors.initials: NH
authors.lastname: Dekker
mesh_terms: D017126:Bacteriophage phi 6 / Q000201:enzymology* / Q000502:physiology; D007700:Kinetics; D009711:Nucleotides / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis* / Q000737:chemistry; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D013696:Temperature; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D009711:Nucleotides; D014764:Viral Proteins; D012313:RNA; D012324:RNA-Dependent RNA Polymerase