Synthesis, Function, and Heterogeneity of snoRNA-Guided Posttranscriptional Nucleoside Modifications in Eukaryotic Ribosomal RNAs.

Ribosomal RNAs contain numerous 2'-O-methylated nucleosides and pseudouridines. Methylation of the 2' oxygen of ribose moieties and isomerization of uridines into pseudouridines are catalyzed by C/D and H/ACA small nucleolar ribonucleoprotein particles, respectively. We review the composition, structure, and mode of action of archaeal and eukaryotic C/D and H/ACA particles. Most rRNA modifications cluster in functionally crucial regions of the rRNAs, suggesting they play important roles in translation. Some of these modifications promote global translation efficiency or modulate translation fidelity. Strikingly, recent quantitative nucleoside modification profiling methods have revealed that a subset of modification sites is not always fully modified. The finding of such ribosome heterogeneity is in line with the concept of specialized ribosomes that could preferentially translate specific mRNAs. This emerging concept is supported by findings that some human diseases are caused by defects in the rRNA modification machinery correlated with a significant alteration of IRES-dependent translation.