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 and Lin He ()
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Rui Song: University of California at Berkeley
Peter Walentek: Genomics and Development, Centre for Integrative Genomics, University of California at Berkeley
Nicole Sponer: University of California at Berkeley
Alexander Klimke: Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany
Joon Sub Lee: University of California at Berkeley
Gary Dixon: University of California at Berkeley
Richard Harland: Genomics and Development, Centre for Integrative Genomics, University of California at Berkeley
Ying Wan: The Third Military Medical University, Chongqing 400038, China
Polina Lishko: University of California at Berkeley
Muriel Lize: University of Goettingen, Goettingen 37073, Germany
Michael Kessel: Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany
Lin He: University of California at Berkeley

Nature, 2014, vol. 510, issue 7503, 115-120

Abstract: 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.

Date: 2014
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DOI: 10.1038/nature13413

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