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.
Highlights
Transcription is the process of polymerase driven synthesis of mRNA from the genome template
Polymerases are delivered to the host cytoplasm associated with the genome template, they initiate transcription only at or near the 39 end of the genome template
The mechanism by which polymerases can redistribute along the genome template when extracted from detergent-disrupted virions in the absence of transcription is not well understood
Summary
Transcription is the process of polymerase driven synthesis of mRNA from the genome template. Polymerases engage their promoters through 3D diffusion [1,2] and have a dissociation constant from their promoters in the range of 40– 60 nM [3,4,5]. Transcription is the first step for efficient replication. Do not rely on cellular polymerases for transcription. Non segmented negative strand (NNS) RNA viruses which include potent human pathogens e.g. Rabies, Ebola and measles, deliver special RNA dependent RNA polymerases to transcribe and replicate their genome template [6,7,8]. Transcription initiates only at or near the 39 end of the genome template [9,10,11] which immediately poses the question of initiation and sustainability of transcription during early stages of infection
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.