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miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110

机译:miR-34 / 449 miRNA是通过抑制cp110进行运动性纤毛发生所必需的

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摘要

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 CpllO, a centriolar protein suppressing cilia assembly. Consistent with this, cpllO 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.
机译:mir-34 / 449家族由位于三个基因组位点的六个同源miRNA组成。 miR-34 / 449 miRNA的冗余及其在多纤毛上皮细胞中的优势表达表明在纤毛形成中具有功能意义。在这里,我们报告所有miR-34 / 449 miRNA缺陷的小鼠表现出产后死亡,不育和粘膜纤毛清除缺陷引起的强烈呼吸功能障碍。在小鼠和非洲爪蟾中,由于有缺陷的基体成熟和顶端对接,miR-34 / 449缺陷的多纤毛细胞(MCC)的纤毛长度和数量显着减少。 miR-34 / 449对纤毛发生的作用至少部分是通过转录后抑制Cp110来实现的,Cp110是一种抑制纤毛蛋白的纤毛装配。与此相一致的是,miR-34 / 449缺陷型MCC中的cpllO敲低可以通过拯救基础体成熟和对接来恢复纤毛发生。总而言之,我们的发现阐明了miR-34 / 449调控运动性纤毛发生的保守细胞和分子机制。

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  • 来源
    《Nature》 |2014年第7503期|115-120|共6页
  • 作者单位

    Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA;

    Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA;

    Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA;

    Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany;

    Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA;

    Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA;

    Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA;

    The Third Military Medical University, Chongqing 400038, China;

    Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA;

    Department of Molecular Oncology, University of Goettingen, Goettingen 37073, Germany;

    Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany;

    Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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