Small Nucleolar RNAs Guide the Ribose Methylations of Eukaryotic rRNAs

Abstract

This chapter provides a progress report on developments that should set the stage for dissecting the rRNA-ribose methylation machinery and for deciphering the role of these modifications in ribosome assembly and function. Interestingly, ribose methylations are far from being uniformly distributed within the universally conserved domains of eukaryotic rRNAs. The finding that small RNA guides specify the sites of ribose methylation in eukaryotic rRNAs raises the issue that RNA cofactors also could be involved in prokaryotes. Prokaryotic rRNAs have considerably fewer ribose methylations than eukaryotic rRNAs, with only 4 sites in E. coli. Two prokaryotic rRNA ribose methylases have been characterized so far that are each specific for a single site in rRNA. The presence of a complex repertoire of site-specific, trans-acting snoRNA guides sufficient to precisely target the modification through the formation of a common canonical duplex structure with the rRNA substrate strongly suggests that the enzymology of the reaction is quite simple, at least as to the variety of protein enzymes involved. snoRNA-guided ribose methylation of rRNA involves the formation of scores of 10-21 bp long intermolecular RNA duplexes along the elongating pre-rRNA transcript in eukaryotes. Analyzing the structure of the methylase(s) and pseudouridine synthase(s) involved in the modification of eukaryotic rRNAs, with particular reference to RNA editing enzymes, also recognizing double-stranded RNA structures could be illuminating.