Figure 3.
Methylase recruitment into RNA genome modification. (A) Predicted minimal requirements for methylation by an ancient methylase. Methylation on hydroxyl oxygen may require AdoMet as methyl group donor, a means of bringing the 2′-hydroxyl and methyl moieties into close contact, and positive charges to facilitate leaving of the hydrogen (see text). The role of the protein enzyme may be simply to augment methylation rather than being directly involved in the catalytic step. (B) SnoRNA-dependent modification of pre-rRNA dates back to the RNA world. As in the modern system, methylation may originally have occurred concurrent with transcription. With the advent of protein synthesis very simple catalysts arose, among these a non-specific dsRNA methylase. The methylase interacted with snoRNAs, being guided or tethered by these to specific sites on the pre-rRNA. The expectation is that this methylase has been retained in the modern eukaryotes and archaea but lost from bacteria. By virtue of its non-specific dsRNA methylating activity, this enzyme is hypothesised to have been recruited into methylation of genomic RNA, improving the stability of the genetic material prior to the origin of DNA. Methylation may initially have been carried out by a ribozyme that associated with each of the methylating snoRNAs, or alternatively methylation could have been carried out by the snoRNAs themselves. Methylase: blue ellipse; methyl groups: red lollipops.