Functional Genomics Unit, Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research (CSIR), Delhi 110 007, India.
RNA. 2010 Jan;16(1):16-25. doi: 10.1261/rna.1688110. Epub 2009 Nov 30.
Eukaryotic gene expression is controlled at the post-transcriptional level by small noncoding RNAs called microRNAs (miRNA). miRNAs play important roles during early development and participate in gene regulatory circuits in the cell. Different high-throughput expression analysis methods including microarrays, bead-based detection, and small RNA cloning have been applied to quantitatively detect miRNAs in various tissues, cell types, and biological conditions. High-throughput expression data was collected from public repositories and processed to create a database of miRNA expression profiles. Several commonly used normalization methods were compared to identify suitable methods for cross-platform comparison of high-throughput miRNA expression data. The database provides interlaboratory and interplatform validated reference expression levels for miRNAs. The normalized expression profiles were validated by querying for well-established features of miRNA expression. Firstly, expression profiles of several tissue-specific miRNAs showed good agreement between the database and previously reported profiles. We have also identified a set of miRNAs that are constitutively expressed across mammalian tissues. Secondly, we used the database to compare the expression patterns of miRNAs belonging to the let-7 family, where the divergence in expression patterns implies that they may have diversified functionally. Lastly, we compared expression profiles of intronic and clustered miRNAs. Expression profiles of intronic miRNAs and clustered miRNAs showed either very good, or in certain cases, very poor correlation with the host gene. Interplatform comparison of miRNA expression profiles thus provides a resource of consensus expression profiles that can be used in the future for studying miRNA function and regulation.
真核生物基因表达在转录后水平受到称为 microRNAs (miRNA) 的小非编码 RNA 的调控。miRNA 在早期发育中发挥重要作用,并参与细胞中的基因调控回路。微阵列、基于珠的检测和小 RNA 克隆等不同的高通量表达分析方法已被用于定量检测各种组织、细胞类型和生物条件下的 miRNA。从公共存储库中收集了高通量表达数据,并进行处理以创建 miRNA 表达谱数据库。比较了几种常用的归一化方法,以确定适用于高通量 miRNA 表达数据跨平台比较的方法。该数据库提供了 miRNA 实验室间和平台间验证的参考表达水平。通过查询 miRNA 表达的既定特征来验证归一化表达谱。首先,数据库中几个组织特异性 miRNA 的表达谱与先前报道的表达谱很好地一致。我们还鉴定了一组在哺乳动物组织中持续表达的 miRNA。其次,我们使用该数据库比较了属于 let-7 家族的 miRNA 的表达模式,其中表达模式的差异表明它们可能具有功能多样化。最后,我们比较了内含子和簇 miRNA 的表达谱。内含子 miRNA 和簇 miRNA 的表达谱与宿主基因具有很好的相关性,或者在某些情况下,相关性很差。miRNA 表达谱的跨平台比较因此提供了共识表达谱资源,可用于未来研究 miRNA 功能和调控。