For a long time it was believed that the nucleotide sequence of every RNA would represent a simple copy of its coding DNA. This axiom of molecular biology, however, has suffered several jolts during the last 25 years. The discovery of intervening or intronic sequences (splicing) and the finding that individual nucleotides can be inserted into and deleted from RNAs (RNA editing) demonstrated that genetic information can be changed at the RNA level. Post‐transcriptional modification of individual ribonucleotides, namely deamination of adenosines and cytidines, can also change the readout of mRNAs (reviewed by Maas and Rich, 2000). Stable cellular RNAs, such as tRNAs, rRNAs and snRNAs, have long been known to contain a large number of post‐transcriptionally synthesized irregular ribonucleotides (Limbach et al., 1994). In tRNAs, the modified nucleotides can facilitate the formation of correct anticodon–codon interaction and thereby increase the efficiency and fidelity of translation (reviewed by Agris, 1996). In rRNAs and spliceosomal snRNAs, methylation of the ribose moiety at the 2′‐hydroxyl group and conversion of uridines into pseudouridine are the most prevalent nucleotide modifications. Since 2′‐O‐methylated nucleotides and pseudouridines are restricted to the functionally essential regions of rRNAs and snRNAs (Reddy et al., 1988; Maden, 1990), they are expected to contribute to the faithful function of the ribosome and the spliceosome. Consistent with this view, lack of ribosomal pseudouridines can reduce the growth rate or confer a selective disadvantage when it is competed against wild‐type ribosomes (Raychaudhuri et al., 1999; Wrzesinski et al., 2000). More tellingly, nucleotide modifications in the 5′‐terminal region of the U2 spliceosomal snRNA are absolutely essential for its function in pre‐mRNA splicing (Yu et al., 1998).