Division of Oncology, Department of Surgery and Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Nucleic Acids Res. 2013 Mar 1;41(5):3339-51. doi: 10.1093/nar/gks1474. Epub 2013 Jan 15.
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression. They are characterized by specific maturation processes defined by canonical and non-canonical biogenic pathways. Analysis of ∼0.5 billion sequences from mouse data sets derived from different tissues, developmental stages and cell types, partly characterized by either ablation or mutation of the main proteins belonging to miRNA processor complexes, reveals 66 high-confidence new genomic loci coding for miRNAs that could be processed in a canonical or non-canonical manner. A proportion of the newly discovered miRNAs comprises mirtrons, for which we define a new sub-class. Notably, some of these newly discovered miRNAs are generated from untranslated and open reading frames of coding genes, and we experimentally validate these. We also show that many annotated miRNAs do not present miRNA-like features, as they are neither processed by known processing complexes nor loaded on AGO2; this indicates that the current miRNA miRBase database list should be refined and re-defined. Accordingly, a group of them map on ribosomal RNA molecules, whereas others cannot undergo genuine miRNA biogenesis. Notably, a group of annotated miRNAs are Dgcr8 independent and DICER dependent endogenous small interfering RNAs that derive from a unique hairpin formed from a short interspersed nuclear element.
MicroRNAs (miRNAs) 是一种小 RNA 分子，可以调控基因表达。它们的特征是具有特定的成熟过程，由经典和非经典生物发生途径定义。对来自不同组织、发育阶段和细胞类型的小鼠数据集的约 5 亿个序列进行分析，这些数据集部分通过主要 miRNA 处理器复合物蛋白的缺失或突变进行了特征描述，结果揭示了 66 个高可信度的新基因组位点，这些位点编码的 miRNA 可以通过经典或非经典方式进行加工。新发现的 miRNA 中有一部分是 mirtrons，我们为此定义了一个新的子类。值得注意的是，其中一些新发现的 miRNA 是从编码基因的非翻译区和开放阅读框产生的，我们对此进行了实验验证。我们还表明，许多注释 miRNA 不具有 miRNA 样特征，因为它们既不受已知加工复合物的加工，也不加载到 AGO2 上；这表明当前的 miRNA miRBase 数据库列表应该进行细化和重新定义。相应地，其中一些位于核糖体 RNA 分子上，而另一些则不能进行真正的 miRNA 生物发生。值得注意的是，一组注释 miRNA 是 Dgcr8 非依赖性和 DICER 依赖性的内源性小干扰 RNA，它们源自由短散布核元件形成的独特发夹结构。
