@article{9a9dd3d843fc43fe9e92d3ff9bb19958,
title = "MiR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110",
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.",
author = "Rui Song and Peter Walentek and Nicole Sponer and Alexander Klimke and Lee, \{Joon Sub\} and Gary Dixon and Richard Harland and Ying Wan and Polina Lishko and Muriel Lize and Michael Kessel and Lin He",
note = "Funding Information: Acknowledgements We thank M. J. Bennett, M. Butler, B. Dynlacht, W. Finkbeiner, P. Kysar, B. Lee, T. Machen, B. Mitchell and J. Wallingford for constructs, technical assistance, stimulating discussions and helpful input. We also thank P. Margolis for careful reading of our manuscript. L.H. acknowledges an R01 and an R21 grant from NCI (R01 CA139067, 1R21CA175560-01), a CIRM new faculty award (RN2-00923-1), a TRDRP research grant (21RT-0133), and a research scholar award from American Cancer Society (ACS, 123339-RSG-12-265-01-RMC). R.S. acknowledges the support ofSiebel postdoctoral fellowship and CIRMpostdoctoralfellowship.P.W.was fundedby the Deutsche Forschungsgemeinschaft (DFG, Wa 3365/1-1), and frog work in the Harland laboratory was funded by NIH grant GM42341. M.L. would like to thank M. Dobbelstein for support and discussions, and was financed by a Dorothea Schloezer Fellowship.",
year = "2014",
doi = "10.1038/nature13413",
language = "English",
volume = "510",
pages = "115--120",
journal = "Nature",
issn = "0028-0836",
number = "7503",
}