Abstract
The phosphoprotein gene of the paramyxoviruses encodes multiple protein products. The P, V, and W proteins are generated by transcriptional slippage. This process results in the insertion of non-templated guanosine nucleosides into the mRNA at a conserved edit site. The P protein is an essential component of the viral RNA polymerase and is encoded by a faithful copy of the gene in the majority of paramyxoviruses. However, in some cases, the non-essential V protein is encoded by default and guanosines must be inserted into the mRNA in order to encode P. The number of guanosines inserted into the P gene can be described by a probability distribution, which varies between viruses. In this article, we review the nature of these distributions, which can be inferred from mRNA sequencing data, and reconstruct the evolutionary history of cotranscriptional editing in the paramyxovirus family. Our model suggests that, throughout known history of the family, the system has switched from a P default to a V default mode four times; complete loss of the editing system has occurred twice, the canonical zinc finger domain of the V protein has been deleted or heavily mutated a further two times, and the W protein has independently evolved a novel function three times. Finally, we review the physical mechanisms of cotranscriptional editing via slippage of the viral RNA polymerase.
Highlights
The Paramyxoviridae are a family of nonsegmented, negative-sense, single-stranded RNA viruses, within the order Mononegavirales (Amarasinghe et al, 2019; Pringle, 1991; Rima et al, 2018)
The nucleocapsid acts as a template for both gene transcription and genome replication, processes that are executed by the viral RNA-dependent RNA-polymerase (RdRp; Whelan et al (2004); Noton and Fearns (2015); Fearns and Plemper (2017); Guseva et al (2019))
The W protein has evolved a novel function associated with its unique C-terminal region on 3 independent occasions (Figures 2 and 4): once for Newcastle disease virus (NDV) (Yang et al, 2019; Karsunke et al, 2019), once for the henipaviral clade comprised of Hendra virus (HeV) and NiV (Shaw et al, 2005; Lo et al, 2009; Edwards et al, 2020), and once for the respiroviral clade composed of BPIV-3, Human parainfluenza virus 3 (HPIV-3), and caprine parainfluenza virus 3 (CPIV-3) (Durbin et al, 1999; Pelet et al, 1991)
Summary
The Paramyxoviridae are a family of nonsegmented, negative-sense, single-stranded RNA viruses, within the order Mononegavirales (Amarasinghe et al, 2019; Pringle, 1991; Rima et al, 2018). Production of multiple proteins results from insertion of one or more non-templated guanosine nucleosides (G) into the mRNA at a conserved edit site, through transcriptional slippage (Vidal et al, 1990b; Hausmann et al, 1999a). This process of base insertion stochastically shifts the reading frame. We note that switching between these two edit modes requires a frameshift mutation in the genome, i.e. during genome replication This mutation must occur at a position upstream of the edit site, but not so far upstream that it disrupts some other function of the encoded P protein. A single nucleotide insertion upstream and proximal to the edit site, accompanied by a single nucleotide deletion elsewhere in the genome, would be sufficient to transit the system from P −→G V −→G W to V −→G W −→G P
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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 call