RNA methyltransferases involved in 5' cap biosynthesis

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

Alternative capping pathways have been invented by certain viruses. For instance, in Alphaviruses, the precursor of cap0 is first methylated to a m 7 G triphosphate and only then connected to the 5 0 end of the RNA. 12 Nonsegmented negative-sense (nsNS) RNA viruses have evolved a different mechanism for mRNA cap formation in that the guanylyltransferase transfers GDP rather than GMP onto the 5 0 end of the RNA and the resulting cap structure is first monomethylated on the ribose of the first transcribed residue (yielding GpppAm structure), and only later the guanosine is methylated to m 7 G. [13] [14] [15] In addition to ribose 2 0 -O-methylation, base moieties of the first transcribed nucleosides may be methylated, thereby increasing the catalog of 5 0 cap structures. In particular, the first adenine nucleoside of the transcript is often methylated at the N 6 position. 16 In Trypanosomes, the fourth uridine residue is also methylated at the N 3 position. The role of these base methylations is unclear, and the enzymes responsible for these modifications remain to be characterized.