Cavaillé Jérôme
Laboratoire de Biologie Moléculaire Eucaryote, Université de Toulouse; UPS and CNRS, LMBE, Toulouse, France.
Wiley Interdiscip Rev RNA. 2017 Jul;8(4). doi: 10.1002/wrna.1417. Epub 2017 Mar 13.
The nucleolus of mammalian cells contains hundreds of box C/D small nucleolar RNAs (SNORDs). Through their ability to base pair with ribosomal RNA precursors, most play important roles in the synthesis and/or activity of ribosomes, either by guiding sequence-specific 2'-O-methylations or by facilitating RNA folding and cleavages. A growing number of SNORD genes 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 (the SNURF-SNRPN domain) and at 14q32 (the DLK1-DIO3 domain) where they are expressed, respectively, only from the paternally and maternally inherited alleles. These placental mammal-specific SNORD genes have many features of the canonical SNORDs that guide 2'-O-methylations, yet they lack obvious complementarity with ribosomal RNAs and, surprisingly, they are processed from large, tandemly repeated genes expressed preferentially in the brain. This review summarizes our understanding of the biology of these peculiar SNORD genes, focusing particularly on SNORD115 and SNORD116 in the SNURF-SNRPN domain. It examines the growing evidence that altered levels of these SNORDs and/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-HT2C serotonin receptor. Finally, the hypothesis that PWS may be a ribosomopathy (ribosomal disease) is also discussed. WIREs RNA 2017, 8:e1417. doi: 10.1002/wrna.1417 For further resources related to this article, please visit the WIREs website.
哺乳动物细胞的核仁包含数百种C/D盒小核仁RNA（SNORD）。通过与核糖体RNA前体碱基配对的能力，大多数SNORD在核糖体的合成和/或活性中发挥重要作用，要么通过引导序列特异性2'-O-甲基化，要么通过促进RNA折叠和切割。最近发现了越来越多功能不明的SNORD基因。有趣的是，其中绝大多数位于人类染色体区域15q11q13（SNURF-SNRPN结构域）和14q32（DLK1-DIO3结构域）的两个大型印记基因簇中，它们分别仅从父本和母本遗传的等位基因中表达。这些胎盘哺乳动物特有的SNORD基因具有许多指导2'-O-甲基化的典型SNORD的特征，但它们与核糖体RNA缺乏明显的互补性，令人惊讶的是，它们是从在大脑中优先表达的大型串联重复基因加工而来的。这篇综述总结了我们对这些特殊SNORD基因生物学的理解，特别关注SNURF-SNRPN结构域中的SNORD115和SNORD116。它研究了越来越多的证据，表明这些SNORD及其宿主基因转录本水平的改变可能是普拉德-威利综合征（PWS；一种以暴饮暴食和肥胖为特征的罕见疾病）以及5-HT2C血清素受体信号传导异常的主要原因。最后，还讨论了PWS可能是一种核糖体病（核糖体疾病）的假说。WIREs RNA 2017, 8:e1417. doi: 10.1002/wrna.1417 有关本文的更多资源，请访问WIREs网站。
