title: Vesicular stomatitis virus polymerase's strong affinity to its template suggests exotic transcription models.
abstract: Vesicular stomatitis virus (VSV) is the prototype for negative sense non segmented (NNS) RNA viruses which include potent human and animal pathogens such as Rabies, Ebola and measles. The polymerases of NNS RNA viruses only initiate transcription at or near the 3' end of their genome template. We measured the dissociation constant of VSV polymerases from their whole genome template to be 20 pM. Given this low dissociation constant, initiation and sustainability of transcription becomes nontrivial. To explore possible mechanisms, we simulated the first hour of transcription using Monte Carlo methods and show that a one-time initial dissociation of all polymerases during entry is not sufficient to sustain transcription. We further show that efficient transcription requires a sliding mechanism for non-transcribing polymerases and can be realized with different polymerase-polymerase interactions and distinct template topologies. In conclusion, we highlight a model in which collisions between transcribing and sliding non-transcribing polymerases result in release of the non-transcribing polymerases allowing for redistribution of polymerases between separate templates during transcription and suggest specific experiments to further test these mechanisms.
authors.affiliation: Department of Physics and Astronomy, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Physics and Astronomy, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Mourad
authors.initials: M
authors.lastname: Bendjennat
authors.affiliation: Department of Physics and Astronomy, University of Utah, Salt Lake City, Utah, United States of America; Center for Cell and Genome Science, University of Utah, Salt Lake City, Utah, United States of America; Department of Biology, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Saveez
authors.initials: S
authors.lastname: Saffarian
mesh_terms: D019295:Computational Biology; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005814:Genes, Viral / Q000235:genetics*; D008957:Models, Genetic; D008958:Models, Molecular; D009010:Monte Carlo Method; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D018116:Vesiculovirus / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases; C512399:L polymerase protein, Vesicular stomatitis-Indiana virus