First Author | Song R | Year | 2014 |
Journal | Nature | Volume | 510 |
Issue | 7503 | Pages | 115-20 |
PubMed ID | 24899310 | Mgi Jnum | J:223064 |
Mgi Id | MGI:5647887 | Doi | 10.1038/nature13413 |
Citation | Song R, et al. (2014) miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110. Nature 510(7503):115-20 |
abstractText | 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. |