Abstract
Rabies virus (RABV) is a causative agent of a fatal neurological disease in humans and animals. The large (L) protein of RABV is a multifunctional RNA-dependent RNA polymerase, which is one of the most attractive targets for developing antiviral agents. A remarkable homology of the RABV L protein to a counterpart in vesicular stomatitis virus, a well-characterized rhabdovirus, suggests that it catalyzes mRNA processing reactions, such as 5′-capping, cap methylation, and 3′-polyadenylation, in addition to RNA synthesis. Recent breakthroughs in developing in vitro RNA synthesis and capping systems with a recombinant form of the RABV L protein have led to significant progress in our understanding of the molecular mechanisms of RABV RNA biogenesis. This review summarizes functions of RABV replication proteins in transcription and replication, and highlights new insights into roles of an unconventional mRNA capping enzyme, namely GDP polyribonucleotidyltransferase, domain of the RABV L protein in mRNA capping and transcription initiation.
Highlights
Rabies virus (RABV) is a nonsegmented negative-strand (NNS) RNA virus belonging to the Lyssavirus genus of the Rhabdoviridae family in the order Mononegavirales.rabies virus (RABV) is transmitted to humans from infected animals, mainly domestic dogs, through their saliva by biting or scratching, and causes an acute, fatal neurological disease, called rabies [2,3,4]
The results showed that a TxΨ (Ψ, aliphatic amino acids) motif (T1174-x-L1176 for RABV, T1161-x-I1163 for vesicular stomatitis virus (VSV)) on the loop is required for RNA capping, whereas a conserved tryptophan (W) residue (W1180 for RABV, W1167 for VSV) is essential for terminal de novo initiation from position 1 of the leader region (Le)(−) promoter (30 -HO-U1 G2 -) to carry out the first phosphodiester bond formation in a template-dependent manner [21]
W residue are dispensable for transcription initiation and capping, respectively [21]. These findings indicate that the putative loop structure extended from the PRNTase domain, named “priming-capping loop”, plays dual roles in transcription initiation and mRNA capping
Summary
Rabies virus (RABV) is a nonsegmented negative-strand (NNS) RNA virus belonging to the Lyssavirus genus of the Rhabdoviridae family in the order Mononegavirales (reviewed in References [1,2,3]). RABV is transmitted to humans from infected animals, mainly domestic dogs, through their saliva by biting or scratching, and causes an acute, fatal neurological disease, called rabies [2,3,4]. Studies on transcription and replication of rhabdoviruses have been carried out mainly using vesicular stomatitis virus (VSV, an arthropod-borne animal vesiculovirus) as a model (reviewed in Reference [8]), because VSV can be safely handled and shows the strongest RNA synthesis activity. Recent advantages in establishing in vitro RNA synthesis and capping assays for RABV have enabled us to elucidate the molecular mechanisms of viral RNA biosynthesis. We discuss roles of RABV replication proteins in transcription and replication, and focus on recent studies regarding unique RABV machineries required for mRNA capping and transcription initiation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: 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.
