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

Rui Song, Peter Walentek, Nicole Sponer, Alexander Klimke, Joon Sub Lee, Gary Dixon, Richard Harland, Ying Wan, Polina Lishko, Muriel Lize, Michael Kessel, Lin He

Nature 2014 Jun 05

filter terms:

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.

Citation

Rui Song, Peter Walentek, Nicole Sponer, Alexander Klimke, Joon Sub Lee, Gary Dixon, Richard Harland, Ying Wan, Polina Lishko, Muriel Lize, Michael Kessel, Lin He. miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110. Nature. 2014 Jun 05;510(7503):115-20