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Nature. 2014 Jun 5;510(7503):115-20. doi: 10.1038/nature13413.

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

Author information

1
1] Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2].
2
1] Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA [2].
3
Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Goettingen 37077, Germany.
4
Division of Cellular and Developmental Biology, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA.
5
Division of Genetics, Genomics and Development, Centre for Integrative Genomics, MCB Department, University of California at Berkeley, Berkeley, California 94705, USA.
6
The Third Military Medical University, Chongqing 400038, China.
7
Department of Molecular Oncology, University of Goettingen, Goettingen 37073, Germany.

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.

PMID:
24899310
PMCID:
PMC4119886
DOI:
10.1038/nature13413
[Indexed for MEDLINE]
Free PMC Article
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