The many faces of small nucleolar RNAs

•snoRNAs canonically guide nucleotide modifications on rRNAs or snRNAs.•Recent genetic screens indicate snoRNA implication in diverse cellular processes.•Some snoRNAs give rise to miRNAs to fine-tune gene expression posttranscriptionally.•At least one snoRNA controls mRNA-editing and likely affects alternative splicing.•There are snoRNAs that display both, canonical and non-canonical activities.

Small nucleolar RNAs (snoRNAs) are a class of evolutionally conserved non-coding RNAs traditionally associated with nucleotide modifications in other RNA species. Acting as guides pairing with ribosomal (rRNA) and small nuclear RNAs (snRNAs), snoRNAs direct partner enzymes to specific sites for uridine isomerization or ribose methylation, thereby influencing stability, folding and protein-interacting properties of target RNAs. In recent years, however, numerous non-canonical functions have also been ascribed to certain members of the snoRNA group, ranging from regulation of mRNA editing and/or alternative splicing to posttranscriptional gene silencing by a yet poorly understood pathway that may involve microRNA-like mechanisms. While some of these intriguing snoRNAs (the so-called orphan snoRNAs) have no sequence complementarity to rRNA or snRNA, others apparently display dual functionality, performing both traditional and newly elucidated functions. Here, we review the effects elicited by non-canonical snoRNA activities.