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MicroRNA filters Hox temporal transcription noise to confer boundary formation in the spinal cord

Author

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  • Chung-Jung Li

    (Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Sciences, National Defense Medical Center
    Institute of Molecular Biology, Academia Sinica)

  • Tian Hong

    (Center for Complex Biological Systems, University of California
    University of California
    Present address: Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, Tennessee 37996, USA)

  • Ying-Tsen Tung

    (Institute of Molecular Biology, Academia Sinica)

  • Ya-Ping Yen

    (Institute of Molecular Biology, Academia Sinica
    Institute of Biotechnology, College of Bio-Resources and Agriculture, National Taiwan University)

  • Ho-Chiang Hsu

    (Institute of Molecular Biology, Academia Sinica)

  • Ya-Lin Lu

    (Institute of Molecular Biology, Academia Sinica)

  • Mien Chang

    (Institute of Molecular Biology, Academia Sinica)

  • Qing Nie

    (Center for Complex Biological Systems, University of California
    University of California)

  • Jun-An Chen

    (Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Sciences, National Defense Medical Center
    Institute of Molecular Biology, Academia Sinica)

Abstract

The initial rostrocaudal patterning of the neural tube leads to differential expression of Hox genes that contribute to the specification of motor neuron (MN) subtype identity. Although several 3′ Hox mRNAs are expressed in progenitors in a noisy manner, these Hox proteins are not expressed in the progenitors and only become detectable in postmitotic MNs. MicroRNA biogenesis impairment leads to precocious expression and propagates the noise of Hoxa5 at the protein level, resulting in an imprecise Hoxa5-Hoxc8 boundary. Here we uncover, using in silico simulation, two feed-forward Hox-miRNA loops accounting for the precocious and noisy Hoxa5 expression, as well as an ill-defined boundary phenotype in Dicer mutants. Finally, we identify mir-27 as a major regulator coordinating the temporal delay and spatial boundary of Hox protein expression. Our results provide a novel trans Hox-miRNA circuit filtering transcription noise and controlling the timing of protein expression to confer robust individual MN identity.

Suggested Citation

  • Chung-Jung Li & Tian Hong & Ying-Tsen Tung & Ya-Ping Yen & Ho-Chiang Hsu & Ya-Lin Lu & Mien Chang & Qing Nie & Jun-An Chen, 2017. "MicroRNA filters Hox temporal transcription noise to confer boundary formation in the spinal cord," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14685
    DOI: 10.1038/ncomms14685
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