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

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.
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