The present review summarizes key progress made in characterizing the small nucleolar RNAs (snoRNAs) of eukaryotic cells. Recent studies have shown snoRNA populations to be substantially more complex than anticipated initially. Many newly discovered snoRNAs are synthesized by an intron-processing pathway, which provides a potential mechanism for coordinating nuclear RNA synthesis. Several snoRNAs and snoRNP proteins are known to be needed for processing of ribosomal RNA, but precise functions remain to be defined. In principle, snoRNAs could have several roles in ribosome synthesis including: folding of pre-rRNA, formation of rRNP substrates, catalyzing RNA cleavages, base modification, assembly of pre-ribosomal subunits, and export of product rRNP particles.

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We have discovered that all known yeast and vertebrate small nucleolar RNAs (snoRNAs), except for the MRP/7-2 RNA, fall into two major classes. One class is defined by conserved boxes C and D and the other by a novel element: a consensus ACA triplet positioned 3 nt before the 3' end of the RNA. A role for the ACA box is snoRNA stability has been established by mutational analysis of a yeast ACA snoRNA (snR 11). Full function of the box depends on the integrity of an adjacent upstream stem. All members of the yeast ACA family are associated with the GAR1 protein. Binding of this or another common small nucleolar ribonucleoprotein particle protein is predicted to be a critical entry point to snoRNA posttranscriptional life, including precise formation of the snoRNA 3' end.

Ten ACA yeast small nucleolar RNAs (snoRNAs) were shown to be required for site-specific synthesis of pseudouridine psi in ribosomal RNA. A common secondary folding motif for the snoRNAs and rRNA target segments predicts that site selection involves: (1) base pairing of the snoRNA with complementary rRNA elements flanking the site of modification, and (2) identification of a uridine located at a near-constant distance from the snoRNA ACA box. The model is supported by mutations showing that: (1) reducing the complementarity between the snoRNA and rRNA disrupts psi formation, and (2) altering the distance between the ACA box and target uridine causes an adjacent uridine to be modified. This discovery implies that most snoRNAs function in targeting nucleotide modification in rRNA: ribose methylation for the box C/D snoRNAs and psi formation for the ACA snoRNAs.

The 3D rRNA modification maps database is the first general resource of information about the locations of modified nucleotides within the 3D structure of the full ribosome, with mRNA and tRNAs in the A-, P- and E-sites. The database supports analyses for several model organisms, including higher eukaryotes, and enables users to construct 3D maps for other organisms. Data are provided for human and plant (Arabidopsis) ribosomes, and for other representative organisms from eubacteria, archaea and eukarya. Additionally, the database integrates information about positions of modifications within rRNA sequences and secondary structures, as well as links to other databases and resources about modifications and their biosynthesis. Displaying positions of modified nucleotides is fully manageable. Views of each modified nucleotide are controlled by individual buttons and buttons also control the visibility of different ribosomal molecular components. A section called ‘Paint Your Own’ enables the user to create a 3D modification map for rRNA from any organism where sites of modification are known. This section also provides capabilities for visualizing nucleotides of interest in rRNA or tRNA, as well as particular amino acids in ribosomal proteins. The database can be accessed at http://people.biochem.umass.edu/fournierlab/3dmodmap/