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Synergistic interactions between Cajal bodies and the miRNA processing machinery

机译:Cajal体系与MiRNA加工机械之间的协同相互作用

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Cajal bodies (CBs) are subnuclear domains involved in the formation of ribonucleoproteins (RNPs) including small nuclear RNPs (snRNPs). CBs associate with specific gene loci, which impacts expression and provides a platform for the biogenesis of the nascent transcripts emanating from these genes. Here we report that CBs can associate with the C19MC microRNA (miRNA) gene cluster, which suggests a role for CBs in the biogenesis of animal miRNAs. The machinery involved in the formation of miRNAs includes the Drosha/DGCR8 complex, which processes primary-miRNA to precursor miRNA. Further processing of precursor miRNA by Dicer and other components generates mature miRNA. To test if CBs influence the expression and formation of miRNAs, we examined two representative miRNAs (miR-520 h and let-7a) in conditions that disrupt CBs. CB disruption correlates with alterations in the level of primary and mature miRNA and the let-7a mRNA target, HMGA2. We have also found that the processing of some small CB-specific RNAs (scaRNAs) is directly mediated by the Drosha/ DGCR8 complex. ScaRNAs form scaRNPs, which play an important role in snRNP formation. Collectively, our results demonstrate that CBs and the miRNA processing machinery functionally interact and together contribute to the biogenesis of miRNAs and snRNPs.
机译:Cajal尸体(CBS)是核核核蛋白(RNP)形成的亚核结构域,包括小核RNPS(SNRNPS)。 CBS与特定基因基因座相关,其影响表达并为从这些基因发出的新生转录物的生物发生的平台。在这里,我们认为CBS可以与C19MC MicroRNA(miRNA)基因簇相关联,这表明CBS在动物miRNA的生物发生中的作用。涉及MiRNA的形成的机器包括DROSHA / DGCR8复合物,其将初级miRNA加工到前体miRNA。进一步处理Dicer和其他组分的前体miRNA,产生成熟miRNA。为了测试CBS影响miRNA的表达和形成,我们在破坏CBS的条件下检查了两个代表性miRNA(miR-520 h和let-7a)。 CB破坏与初级和成熟miRNA水平和Let-7a mRNA靶,HMGA2的改变相关。我们还发现,一些小Cb特异性RNA(Scarnas)的处理直接由DROSHA / DGCR8复合物介导。疤痕形成疤痕,这在SNRNP形成中发挥着重要作用。统称,我们的结果表明CBS和MiRNA加工机械功能相互作用,共同有助于MiRNA和SNRNP的生物发生。

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