Abstract
SR/RS domains are found in almost all eukaryotic genomes from C. elegans to human. These domains are thought to mediate interactions between proteins but also between proteins and RNA in complex networks associated with mRNA splicing, chromatin structure, transcription, cell cycle and cell structure. A precise and tight regulation of their function is achieved through phosphorylation of a number of serine residues within the SR/RS motifs by the Serine-Arginine protein kinases (SRPKs) that lead to delicate structural alterations. Given that coronavirus N proteins also contain SR/RS domains, we formulate the hypothesis that the viruses exploit the properties of these motifs to promote unpacking of viral RNA and virion assembly.
Highlights
Coronaviruses (CoVs) have a single-stranded positive-sense RNA genome covered by an enveloped structure
The N protein of coronaviruses is structurally organized into two domains, the N-terminal domain (NTD) and C-terminal domain (CTD), which are separated by a flexible linker (Figure 1)
We propose that phosphorylation by Serine-Arginine protein kinases (SRPKs) at the very early stage of infection and the subsequent displacement of N protein molecules from the 5 end of the viral RNA, in the form of an unzipping mechanism, would allow repeated rounds of genome translation, progressive formation of Double-Membrane Vesicles (DMVs) and as a result progressive assembly of replicase complexes in restricted loci of the endoplasmic reticulum
Summary
Coronaviruses (CoVs) have a single-stranded positive-sense RNA genome covered by an enveloped structure. The order of genes (5 –3 ) contained in their RNA genome is as follows: replicase ORF1a/b, spike (S), envelope (E), membrane (M), and nucleocapsid (N) (McBride et al, 2014; Wu et al, 2020). The two-third of the RNA genome is covered by ORF1a/b encoding two overlapping replicase proteins in the form of polyproteins, which are proteolytically processed by virally encoded proteases into the mature non-structural proteins, while the last third of the genone encodes the four structural proteins, S, M, E, and N and accessory proteins (Wu et al, 2020). Of the four structural proteins, the nucleocapsid protein N is the one that is responsible for packaging the viral RNA (Chang et al, 2014; McBride et al, 2014). We gather evidence from the literature and present a potential mechanism by which N protein-genomic RNA interactions may be governed by phosphorylation/dephosphorylation events spatially and temporally regulated
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