the base (nucleotide) targeted for modification in the pre-RNA molecule. This enables the snoRNP to recognise and bind to the target RNA. Once the snoRNP has bound to the target site, the associated proteins are in the correct physical location to catalyse the chemical modification of the target base. snoRNA guide families The two different types of rRNA modification (methylation and pseudouridylation) are directed by two different families of snoRNAs. These families of snoRNAs are referred to as antisense C/D box and H/ACA box snoRNAs based on the presence of conserved sequence motifs in the snoRNA. There are exceptions, but as a general rule C/D box members guide methylation and H/ACA members guide pseudouridylation. The members of each family may vary in biogenesis, structure, and function, but each family is classified by the following generalised characteristics. For more detail, see review. SnoRNAs are classified under small nuclear RNA in MeSH. The HGNC, in collaboration with snoRNABase and experts in the field, has approved unique names for human genes that encode snoRNAs. C/D box C/D box snoRNAs contain two short conserved sequence motifs, C (RUGAUGA) and D (CUGA), located near the 5′ and 3′ ends of the snoRNA, respectively. Short regions (~ 5 nucleotides) located upstream of the C box and downstream of the D box are usually base complementary and form a stem-box structure, which brings the C and D box motifs into close proximity. This stem-box structure has been shown to be essential for correct snoRNA synthesis and nucleolar localization. Many C/D box snoRNA also contain an additional less-well-conserved copy of the C and D motifs (referred to as C' and D') located in the central portion of the snoRNA molecule. A conserved region of 10–21 nucleotides upstream of the D box is complementary to the methylation site of the target RNA and enables the snoRNA to form an RNA duplex with the RNA. The nucleotide to be modified in the target RNA is usually located at the 5th position upstream from the D box (or D' box). C/D box snoRNAs associate with four evolutionary conserved and essential proteins—fibrillarin (Nop1p), NOP56, NOP58, and SNU13 (15.5-kD protein in eukaryotes; its archaeal homolog is L7Ae)—which make up the core C/D box snoRNP. There exists a eukaryotic C/D box snoRNA (snoRNA U3) that has not been shown to guide 2′-O-methylation. Instead, it functions in rRNA processing by directing pre-rRNA cleavage. H/ACA box