The nucleolar compartment of the nucleus of eukaryotic cells contains the abundant protein fibrillarin and a large collection of fibrillarin associated C/D box snoRNAs. Most all of these RNAs function by employing a common helical ruler mechanism to direct 2'-O-ribose methylation to specific sites in 18S or 28S rRNA. The methylations may be important determinants in the folding and the stabilization of the structure of the rRNAs and their assembly into mature ribosomal subunits. Direct cloning of RNAs associated with the archaeal homolog of fibrillarin and computer searches of archaeal genome sequences have revealed the presence of C/D box sno-like RNAs in at least six widely divergent genera from both the crenarchaeote and euryarchaeote branches of the archaeal domain.
Analysis of archaeal C/D box sRNAs relative to eukaryotic snoRNAs reveals interesting structure-function features. The archaeal sRNAs are small, generally 50-60 nt in length, whereas human and yeast methylation guide snoRNAs average roughly 75 and 100 nt, respectively. A much larger proportion of archaeal sRNAs appear to have the ability to guide methylation from both D and D' boxes as ``double guides'', particularly the Pyrococcal sRNAs. Based on program predictions and comparative sequence analysis among Pyrococcal families, we estimate at least 50% of archaeal sRNAs guide methylation using both 5' and 3' guide regions, whereas only 20% of human and yeast snoRNAs have been reported to be double-guides [Kiss-Laszlo et al., 1996,Lowe & Eddy, 1999]. Often, double guides target sites that are within the same target RNA (i.e., 16S or 23S rRNA) and often they are closely linked within the target RNA. For example, Sac sR12 appears to direct methylation using D' and D box guides to positions G1114 and A1134 in 23S rRNA. This is in contrast to yeast snoRNA double guides, in which there is no apparent correlation between molecules targeted by the same snoRNA.