In eukaryotes and archaea, 2΄-O-methylation is catalysed by box C/D snoRNPs and the related box C/D sRNPs, respectively (18). The RNA components of these complexes (snoRNAs and sRNAs) contain a conserved C/D motif at the termini of the RNA and an internal C΄/D΄ motif (Figure 1A). Both motifs share the same consensus, although the C/D motif is part of a stem-internal loop-stem structure, also known as a K-turn (Figure 1A), while the C΄/D΄ motif often forms a stem-loop structure, lacking stem I, which is known as a K-loop (18). The snoRNA/sRNA functions as a guide for modification by base-pairing to the target site with the nucleotide in the snoRNA–rRNA duplex five base-pairs upstream of box D or D΄ being 2΄-O-methylated (Figure 1A; (18)). The eukaryotic snoRNPs contain four common core proteins, Snu13 (15.5K in humans), Nop56, Nop58 and Nop1 (fibrillarin) while the archaeal complexes are associated with L7Ae, Nop5 and fibrillarin. Fibrillarin/Nop1 is the active methyltransferase subunit and L7Ae/Snu13 are the primary RNA-binding proteins that recognise the sheared GA base-pairs at the centre of the C/D and C΄/D΄ motifs (Figure 1B; (18)). Archaeal Nop5 homodimerises and this homodimer forms a structural scaffold that links the proteins bound to the C/D and C΄/D΄ motifs (19–22). In eukaryotes, Nop56 and Nop58, which are homologous to Nop5 are predicted to form a heterodimer that bridges the complex and contacts the C΄/D΄ and C/D motifs, respectively (Figure 1B).