Box C/D small nucleolarRNAgenes and the Prader‐Willi syndrome: a complex interplay

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Abstract
The nucleolus of mammalian cells contains hundreds of box C/D small nucleolarRNAs(SNORDs). Through their ability to base pair with ribosomalRNAprecursors, most play important roles in the synthesis and/or activity of ribosomes, either by guiding sequence‐specific 2′‐O‐methylations or by facilitatingRNAfolding and cleavages. A growing number ofSNORDgenes with elusive functions have been discovered recently. Intriguingly, the vast majority of them are located in two large, imprinted gene clusters at human chromosome region 15q11q13 (theSNURF–SNRPNdomain) and at 14q32 (theDLK1–DIO3domain) where they are expressed, respectively, only from the paternally and maternally inherited alleles. These placental mammal‐specificSNORDgenes have many features of the canonicalSNORDsthat guide 2′‐O‐methylations, yet they lack obvious complementarity with ribosomalRNAsand, surprisingly, they are processed from large, tandemly repeated genes expressed preferentially in the brain. This review summarizes our understanding of the biology of these peculiarSNORDgenes, focusing particularly onSNORD115andSNORD116in theSNURF–SNRPNdomain. It examines the growing evidence that altered levels of theseSNORDsand/or their host‐gene transcripts may be a primary cause of Prader‐Willi syndrome (PWS; a rare disorder characterized by overeating and obesity) as well as abnormalities in signaling through the 5‐HT2Cserotonin receptor. Finally, the hypothesis thatPWSmay be a ribosomopathy (ribosomal disease) is also discussed.WIREs RNA2017, 8:e1417. doi: 10.1002/wrna.1417This article is categorized under: Translation > Ribosome Biogenesis RNA Processing > RNA Editing and Modification RNA in Disease and Development > RNA in Disease
Funding Information
  • Foundation for Prader-Willi Research
  • Fondation pour la Recherche Médicale (DEQ20160334936)

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