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

MPG-Autoren
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Klimke,  A.
Research Group of Developmental Biology, MPI for biophysical chemistry, Max Planck Society;

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Kessel,  M.
Research Group of Developmental Biology, MPI for biophysical chemistry, Max Planck Society;

Externe Ressourcen

http://www.nature.com/nature/journal/v510/n7503/pdf/nature13413.pdf
(Verlagsversion)

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Zitation

Song, R., Walentek, P., Sponer, N., Klimke, A., Lee, J. S., Dixon, G., et al. (2014). miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110. Nature, 510(7503), 115-120. doi:10.1038/nature13413.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-0019-BBA3-0
Zusammenfassung
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.