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

<jats:p>A myriad of structurally and functionally diverse noncoding <jats:styled-content style="fixed-case">RNAs</jats:styled-content> (<jats:styled-content style="fixed-case">ncRNAs</jats:styled-content>) have recently been implicated in numerous human diseases including cancer. Small nucleolar <jats:styled-content style="fixed-case">RNAs</jats:styled-content> (<jats:styled-content style="fixed-case">snoRNAs</jats:styled-content>), the most abundant group of intron‐encoded <jats:styled-content style="fixed-case">ncRNAs</jats:styled-content>, are classified into two families (box C/D <jats:styled-content style="fixed-case">snoRNAs</jats:styled-content> and box H/<jats:styled-content style="fixed-case">ACA snoRNAs</jats:styled-content>) and are required for post‐transcriptional modifications on ribosomal <jats:styled-content style="fixed-case">RNA</jats:styled-content> (<jats:styled-content style="fixed-case">rRNA</jats:styled-content>). There is now a growing appreciation that nucleotide modifications on <jats:styled-content style="fixed-case">rRNA</jats:styled-content> may impart regulatory potential to the ribosome; however, the functional consequence of site‐specific <jats:styled-content style="fixed-case">snoRNA</jats:styled-content>‐guided modifications remains poorly defined. Discovered almost 20 years ago, H/<jats:styled-content style="fixed-case">ACA snoRNAs</jats:styled-content> are required for the conversion of specific uridine residues to pseudouridine on <jats:styled-content style="fixed-case">rRNA</jats:styled-content>. Interestingly, recent reports indicate that the levels of subsets of H/<jats:styled-content style="fixed-case">ACA snoRNAs</jats:styled-content> required for pseudouridine modifications at specific sites on <jats:styled-content style="fixed-case">rRNA</jats:styled-content> are altered in several diseases, particularly cancer. In this review, we describe recent advances in understanding the downstream consequences of H/<jats:styled-content style="fixed-case">ACA snoRNA</jats:styled-content>‐guided modifications on ribosome function, discuss the possible mechanism by which H/<jats:styled-content style="fixed-case">ACA snoRNAs</jats:styled-content> may be regulated, and explore prospective expanding functions of H/<jats:styled-content style="fixed-case">ACA snoRNAs</jats:styled-content>. Furthermore, we discuss the potential biological implications of alterations in H/<jats:styled-content style="fixed-case">ACA snoRNA</jats:styled-content> expression in several human diseases. <jats:italic>WIREs RNA</jats:italic> 2015, 6:173–189. doi: 10.1002/wrna.1266</jats:p><jats:p>This article is categorized under: <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Translation > Translation Regulation</jats:p></jats:list-item> <jats:list-item><jats:p>RNA Processing > RNA Editing and Modification</jats:p></jats:list-item> <jats:list-item><jats:p>RNA in Disease and Development > RNA in Disease</jats:p></jats:list-item> </jats:list></jats:p>