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

A myriad of structurally and functionally diverse noncoding 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 on ribosomal RNA (rRNA). There is now a growing appreciation that nucleotide modifications on rRNA may impart regulatory potential to the ribosome; 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 discuss the potential biological implications of alterations in H/ACA snoRNA expression in several human diseases.