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

regarding their RNA capping pathway, it only succeeded in predicting 2'OMTase, while a second non-canonical RNA-cap N7-guanine MTase was later structurally and functionally characterized [4, [10] [11] [12] [13] [14] . Until then, viral MTases matched a specific structural architecture, the Rossmann fold (RF), which possess a unique interaction geometry that represents a fingerprint of common ancestry. The discovery of a non-Rossmann fold (NRF) MTase unveiled the limitation of annotating "dark proteome" data [15] , lacking structural counterparts. In Nidovirales, enzyme activities have been experimentally evidenced only for coronaviruses and roniviruses [16] . The putative first step of the Nidovirales RNA capping pathway, involving a 5'-triphosphatase, is uncertain: such activity exists in the Coronavirus helicase (nsp13, [17] ), but its involvement in RNA capping has not been directly demonstrated. The guanylyltransferase also remains unknown: A nidovirus RdRp-associated nucleotidyltransferase (NiRAN) activity was found to be associated to the N-terminus of the arterivirus nsp9 RdRp [18] , but its role in arterivirus RNA synthesis, if any, remains to be determined.