Viruses know more than one way to don a cap

Capping of mRNA is an early posttranscriptional event, unique to eukaryotes, that strongly influences subsequent processing, nuclear export, stability, and translation of mRNA. Accordingly, viruses of eukaryotes, whether they reside in the nucleus or cytoplasm, must solve the capping problem for efficient replication. In a recent issue of PNAS, Ogino et al. (1) demonstrate a distinct mechanism used by vesicular stomatitis virus (VSV), and likely other nonsegmented negative strand RNA viruses (Mononegavirales), to cap the 5′ end of mRNA. The finding is of interest from biochemical and evolutionary perspectives and exemplifies the diverse ways that viruses adapt to their hosts. A cap, consisting of a 7-methylguanosine (m7G) linked to the 5′ end of the transcript by a 5′-5′ triphosphate bridge [m7G(5′)ppp(5′)N- or m7G(5′)ppp(5′)Nm in which Nm is a 2′-O methylated nucleoside], was identified in viral and mammalian mRNA 35 years ago and was subsequently found to be ubiquitous in eukaryotes and their viruses with a few exceptions among the latter (2–4). The enzymology of cap biogenesis, originally deduced for vaccinia virus (5–8), also pertains to eukaryotes (9) (Fig. 1A). In this conventional pathway, …