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

Author

Listed:
  • 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)

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.

Suggested 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, 2014. "miR-34/449 miRNAs are required for motile ciliogenesis by repressing cp110," Nature, Nature, vol. 510(7503), pages 115-120, June.
    • Handle: RePEc:nat:nature:v:510:y:2014:i:7503:d:10.1038_nature13413
    DOI: 10.1038/nature13413
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    Cited by:

    1. Andrea Flesken-Nikitin & Coulter Q. Ralston & Dah-Jiun Fu & Andrea J. Micheli & Daryl J. Phuong & Blaine A. Harlan & Christopher S. Ashe & Amanda P. Armstrong & David W. McKellar & Sangeeta Ghuwalewal, 2024. "Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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