RNA methyltransferases involved in 5' cap biosynthesis

Byszewska, Magdalena; Smietanski, Miroslaw; Purta, Elzbieta; Bujnicki, Janusz M

In Flaviviruses (positive-sense, single-stranded RNA viruses), an RFM domain with a similar dual methyltransferase function was identified. In a non-structural protein 5, the N-terminus was first unambiguously characterized as a cap1 (2 0 -O-ribose) methyltransferase. Later, it was shown that this domain takes part also in cap0 (m 7 G) methylation using the same SAM-binding site during cap synthesis. 57, 58 Interestingly, in these viruses, the order of methylation is different than in Mononegavirales, as cap0 methylation precedes cap1 methylation. Several structures were determined for the flavivirus cap methyltransferases known or predicted to be bifunctional, including Dengue, 59 West Nile, 60 Wesselbron, 61 Meaban, 62 and Murray Valley encephalitis 63 viruses and they all revealed high similarity to the cap1 methyltransferases, and little if any similarity to the classical cap0 methyltransferases. It should be noted that these methyltransferases share a similar cap-binding platform structure with VP39 and human CMTr1 enzymes (a platform formed by N-and C-terminal extensions); however, the orientation of the bound guanosine residue suggests that their mode of cap-recognition is different from both poxvirus and human enzymes (Fig. 3) .