Identification of a Nidovirales Orf1a N7-guanine cap Methyltransferase signature-sequence as a genetic marker of large genome Tobaniviridae

François Ferron; Humberto Julio Debat; Etienne Decroly; Bruno Canard

As indicated above, many Nidovirales members, such as SARS-CoV, stand out because they possess a NRF-MTase, participating to cap N7-guanine methylation, embedded at the Cterminus of their nsp14 gene product. It have been previously reported that the N7-guanine-MTase domain is not uniformly present in nsp14-containing nidoviruses [21] . The phylogenetic tree of Figure 1 reports our findings, and confirms that coronaviruses and most mesoniviruses only possess signature-sequences lining the SAM binding site seen in the nsp14 MTase domain structure. Conversely, the other members of the Nidovirales order (Arteriviridae, Medionivirdae, Roniviridae, Euroniviridae, Abyssoviridae, Mononiviridae and Tobaniviridae) do not seem to embed any nsp14-like NRF-MTase. Two notable exceptions are apparent: First, the unique members of Abyssoviridae, Mononiviridae do possess a MTase signature-sequence at the C-terminus of their nsp14-like gene, (i.e., fused to the ExoN domain). Curiously, though, this MTase is readily detectable using HH-Pred as a RF-MTase which does qualify neither as a K-D-K-E 2'-O MTase nor as a N7-guanine MTase (see below). Second, the Fathead Minnow nidovirus 1, belonging to the Tobaniviridae, is also an exception as we detected a nsp14-like NRF MTase at the expected genomic Orf1b position. Against, based on the homology with the nsp14-like MTase domain characterized by the absence of K-D-K-E catalytic residue and NRF folding, we hypothesize that these enzymes might play a role in guanine N7 methylation of the RNA cap structure. Apart from coronaviruses and most mesoniviruses, how nidoviruses methylate their RNA-cap N7-guanine position is thus still unclear.