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

  • Author(s): Song, Rui
  • Walentek, Peter
  • Sponer, Nicole
  • Klimke, Alexander
  • Lee, Joon Sub
  • Dixon, Gary
  • Harland, Richard
  • Wan, Ying
  • Lishko, Polina
  • Lize, Muriel
  • Kessel, Michael
  • He, Lin
  • et al.
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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