Division of Hematology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Biochem J. 2010 Jul 1;429(1):33-41. doi: 10.1042/BJ20091898.
snoRNAs (small nucleolar RNAs) are key components of snoRNP (small nucleolar ribonucleoprotein) particles involved in modifying specific residues of ribosomal and other RNAs by pseudouridylation (H/ACA snoRNAs) or methylation (C/D snoRNAs). They are encoded within the introns of host genes, which tend to be genes whose products are involved in ribosome biogenesis or function. Although snoRNPs are abundant, ubiquitous and their components highly conserved, information concerning their expression during development or how their expression is altered in diseased states is sparse. To facilitate these studies we have developed a snoRNA microarray platform for the analysis of the abundance of snoRNAs in different RNA samples. In the present study we show that the microarray is sensitive and specific for the detection of snoRNAs. A mouse snoRNA microarray was used to monitor changes in abundance of snoRNAs after ablation of dyskerin, an H/ACA snoRNA protein component, from mouse liver, which causes a decrease in ribosome production. H/ACA snoRNAs were decreased in abundance in these livers while, unexpectedly, C/D snoRNAs were increased. The increase in C/D snoRNAs corresponded with an increase in the abundance of the mRNAs transcribed from snoRNA host genes, suggesting the increase may be part of a cellular response to defective ribosome synthesis.
snoRNAs(小核仁 RNA)是 snoRNP(小核仁核糖核蛋白)颗粒的关键组成部分,参与通过假尿嘧啶化(H/ACA snoRNAs)或甲基化(C/D snoRNAs)修饰核糖体和其他 RNA 的特定残基。它们编码在宿主基因的内含子中,这些基因往往是其产物参与核糖体生物发生或功能的基因。尽管 snoRNPs 丰富、普遍存在且其成分高度保守,但有关其在发育过程中的表达情况或在疾病状态下其表达如何改变的信息却很少。为了促进这些研究,我们开发了 snoRNA 微阵列平台,用于分析不同 RNA 样本中 snoRNAs 的丰度。在本研究中,我们表明该微阵列对 snoRNAs 的检测具有敏感性和特异性。使用小鼠 snoRNA 微阵列监测了敲除小鼠肝脏中的 dyskerin(一种 H/ACA snoRNA 蛋白成分)后 snoRNAs 丰度的变化,这会导致核糖体产生减少。这些肝脏中的 H/ACA snoRNAs 丰度降低,而出人意料的是,C/D snoRNAs 增加。C/D snoRNAs 的增加与从 snoRNA 宿主基因转录的 mRNA 丰度的增加相对应,表明这种增加可能是细胞对核糖体合成缺陷的反应的一部分。