Nature2014-06-16 5:12 PM

微RNA与呼吸病的关系 miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110

论文摘要 

miR-34/449家族的6个微RNA (miRNA)非常相似。它们的功能重叠,所以难以确定它们具体的生物学作用。Lin He及同事发表了从缺少所有6个miR-34/449 miRNA的小鼠获得的数据。这些动物表现出频发的产后死亡、呼吸功能失常(与一些“原发性纤毛运动障碍”患者的呼吸系统并发症相似)和不育。这些现象的主要深层缺陷是呼吸道细胞的纤毛较短和较少,这在很大程度上是由于与顶膜对接的基体(basal body)所存在的缺陷。在作者所识别出的57个潜在miR-34/449 miRNA目标中,一个是Cp110。它是一个中心粒蛋白,抑制纤毛聚集。有趣的是,研究人员已经发现了与呼吸病相关的异常Cp110水平。

Abstract 

The mir-34/449 family consists of six homologous miRNAs at three genomic loci. Redundancy of miR-34/449 miRNAs and their dominant expression in multiciliated epithelia suggest a functional significance in ciliogenesis. Here we report that mice deficient for all miR-34/449 miRNAs exhibited postnatal mortality, infertility and strong respiratory dysfunction caused by defective mucociliary clearance. In both mouse and Xenopus, miR-34/449-deficient multiciliated cells (MCCs) exhibited a significant decrease in cilia length and number, due to defective basal body maturation and apical docking. The effect of miR-34/449 on ciliogenesis was mediated, at least in part, by post-transcriptional repression of Cp110, a centriolar protein suppressing cilia assembly. Consistent with this, cp110 knockdown in miR-34/449-deficient MCCs restored ciliogenesis by rescuing basal body maturation and docking. Altogether, our findings elucidate conserved cellular and molecular mechanisms through which miR-34/449 regulate motile ciliogenesis.

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