Small RNAs with big implications: new insights into H/ACA snoRNA function and their role in human disease

Mary McMahon, Adrian Contreras, Davide Ruggero
2014 Wiley Interdisciplinary Reviews - RNA  
A myriad of structurally and functionally diverse non-coding RNAs (ncRNAs) have recently been implicated in numerous human diseases including cancer. Small nucleolar RNAs (snoRNAs), the most abundant group of intron-encoded ncRNAs, are classified into two families (box C/D snoRNAs and box H/ACA snoRNAs) and are required for post-transcriptional modifications of ribosomal RNA (rRNA). There is now a growing appreciation that nucleotide modifications on rRNA may impart regulatory potential to the
more » ... ibosome, however the functional consequence of site-specific snoRNA-guided modifications remains poorly defined. Discovered almost 20 years ago, H/ACA snoRNAs are required for the conversion of specific uridine residues to pseudouridine on rRNA. Interestingly, recent reports indicate that the levels of subsets of H/ACA snoRNAs required for pseudouridine modifications at specific sites on rRNA are altered in several diseases, particularly cancer. In this review, we describe recent advances in understanding the downstream consequences of H/ACA snoRNA-guided modifications on ribosome function, discuss the possible mechanism by which H/ACA snoRNAs may be regulated, and explore prospective expanding functions of H/ACA snoRNAs. Furthermore, we will discuss the potential biological implication of alterations in H/ACA snoRNA expression in several human diseases. The RNA component of the ribosome, ribosomal RNA (rRNA), undergoes numerous sitespecific post-transcriptional nucleotide modifications, several of which are located within functionally important regions of the ribosome (1, 2). Two predominant types of rRNA modifications involve the addition of a methyl group to the 2′-hydroxyl group of a ribose residue (2′-O-methylation) and the isomerization of uridine to pseudouridine (Ψ), a process known as pseudouridylation. In eukaryotes, both types of modifications occur in the nucleolus and require hundreds of small nucleolar RNAs (snoRNAs) (3), ranging in length from 60-300 nucleotides, as well as multicomponent protein complexes, collectively
doi:10.1002/wrna.1266 pmid:25363811 pmcid:PMC4390053 fatcat:mooznxjctbcffev7w53hrhv75i