Methyltransferases of Riboviria

Abstract

Many viruses from the realm Riboviria infecting eukaryotic hosts encode protein domains with sequence similarity to S-adenosylmethionine-dependent methyltransferases. These protein domains are thought to be involved in methylation of the 5′-terminal cap structures in virus mRNAs. Some methyltransferase-like domains of Riboviria are homologous to the widespread cellular FtsJ/RrmJ-like methyltransferases involved in modification of cellular RNAs; other methyltransferases, found in a subset of positive-strand RNA viruses, have been assigned to a separate “Sindbis-like” family; and coronavirus-specific Nsp13/14-like methyltransferases appeared to be different from both those classes. The representative structures of proteins from all three groups belong to a specific variety of the Rossmann fold with a seven-stranded β-sheet, but it was unclear whether this structural similarity extends to the level of conserved sequence signatures. Here I survey methyltransferases in Riboviria and derive a joint sequence alignment model that covers all groups of virus methyltransferases and subsumes the previously defined conserved sequence motifs. Analysis of the spatial structures indicates that two highly conserved residues, a lysine and an aspartate, frequently contact a water molecule, which is located in the enzyme active center next to the methyl group of S-adenosylmethionine cofactor and could play a key role in the catalytic mechanism of the enzyme. Phylogenetic evidence indicates a likely origin of all methyltransferases of Riboviria from cellular RrmJ-like enzymes and their rapid divergence with infrequent horizontal transfer between distantly related viruses.

Mapping glycoprotein structure reveals defining events in the evolution of theFlaviviridae

“…Our evolutionary reconstruction suggests that this ancestor possibly contained core NS3/NS5 proteins and potentially an MTase. Although the absence of RrmJ-like methyltransferases, such as those found in the Flaviviridae, in other Kitrinoviricota members 38 , hints that MTase might have been acquired at the base of lineage one. It remains unclear whether this progenitor possessed a viral envelope, therefore necessitating entry glycoproteins, although it is noteworthy that all Kitrinoviricota members (n = 20) with the exception of Togaviridae and Matonaviridae are non-enveloped.…”

Methyltransferase-like (METTL) homologues participate in Nicotiana benthamiana antiviral responses

“…m 6 A affects a variety of RNA metabolic processes in eukaryotic cells, 13 and is evolutionary conserved in divergent plant taxa. 9 Some RNA modifications play a significant role in antiviral responses, 11 , 18 , 40 , 41 among them m 6 A is increasingly recognized as a key regulatory component of plant virus immunity. 10 , 25 , 26 …”

“…MTase domains recur in diverse viral taxa, 18 but their contribution in m 6 A deposition and cellular epitranscriptomic dynamics is currently unknown. Several studies nonetheless showed that cellular METTLs affect viral infection of eukaryotic hosts.…”

Predicted Membrane-Associated Domains in Proteins Encoded by Novel Monopartite Plant RNA Viruses Related to Members of the Family Benyviridae

“…This fact may lead to negative results in CDD searches for Reclovirid replicases. Importantly, a recent general comparative analysis of Riboviria-encoded methyltransferases [12] clearly indicates that the methyltransferase domains are characteristic for replicases of Benyviridae and particularly the genus Benyvirus. Interestingly, in some cases, the possible methyltransferase domain of Reclovirid replicases is preceded by membrane-embedded protein segments that are not present in annotated members of the family Benyviridae (Supplementary Figure S1).…”