Gstir Ronald, Schafferer Simon, Scheideler Marcel, Misslinger Matthias, Griehl Matthias, Daschil Nina, Humpel Christian, Obermair Gerald J, Schmuckermair Claudia, Striessnig Joerg, Flucher Bernhard E, Hüttenhofer Alexander
Division of Genomics and RNomics, Innsbruck Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.
RNA Biology Group, Institute for Genomics and Bioinformatics, Graz University of Technology, 8010 Graz, Austria.
RNA. 2014 Dec;20(12):1929-43. doi: 10.1261/rna.047225.114. Epub 2014 Oct 24.
We have generated a novel, neuro-specific ncRNA microarray, covering 1472 ncRNA species, to investigate their expression in different mouse models for central nervous system diseases. Thereby, we analyzed ncRNA expression in two mouse models with impaired calcium channel activity, implicated in Epilepsy or Parkinson's disease, respectively, as well as in a mouse model mimicking pathophysiological aspects of Alzheimer's disease. We identified well over a hundred differentially expressed ncRNAs, either from known classes of ncRNAs, such as miRNAs or snoRNAs or which represented entirely novel ncRNA species. Several differentially expressed ncRNAs in the calcium channel mouse models were assigned as miRNAs and target genes involved in calcium signaling, thus suggesting feedback regulation of miRNAs by calcium signaling. In the Alzheimer mouse model, we identified two snoRNAs, whose expression was deregulated prior to amyloid plaque formation. Interestingly, the presence of snoRNAs could be detected in cerebral spine fluid samples in humans, thus potentially serving as early diagnostic markers for Alzheimer's disease. In addition to known ncRNAs species, we also identified 63 differentially expressed, entirely novel ncRNA candidates, located in intronic or intergenic regions of the mouse genome, genomic locations, which previously have been shown to harbor the majority of functional ncRNAs.
我们构建了一种新型的、神经特异性ncRNA微阵列，涵盖1472种ncRNA，以研究它们在中枢神经系统疾病不同小鼠模型中的表达。因此，我们分析了两种钙通道活性受损的小鼠模型中的ncRNA表达，这两种模型分别与癫痫或帕金森病有关，以及一种模拟阿尔茨海默病病理生理特征的小鼠模型。我们鉴定出了一百多种差异表达的ncRNA，它们要么来自已知的ncRNA类别，如miRNA或snoRNA，要么代表全新的ncRNA种类。钙通道小鼠模型中几种差异表达的ncRNA被鉴定为miRNA，其靶基因参与钙信号传导，因此提示钙信号对miRNA的反馈调节。在阿尔茨海默病小鼠模型中，我们鉴定出两种snoRNA，它们在淀粉样斑块形成之前表达失调。有趣的是，在人类脑脊液样本中可以检测到snoRNA的存在，因此有可能作为阿尔茨海默病的早期诊断标志物。除了已知的ncRNA种类，我们还鉴定出63种差异表达的全新ncRNA候选物，它们位于小鼠基因组的内含子或基因间区域，这些基因组位置以前已被证明含有大多数功能性ncRNA。
