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

Chung-Jung Li, Tian Hong, Ying-Tsen Tung, Ya-Ping Yen, Ho-Chiang Hsu, Ya-Lin Lu, Mien Chang, Qing Nie () and Jun-An Chen ()
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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
Tian Hong: Center for Complex Biological Systems, University of California
Ying-Tsen Tung: Institute of Molecular Biology, Academia Sinica
Ya-Ping Yen: Institute of Molecular Biology, Academia Sinica
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
Jun-An Chen: Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Sciences, National Defense Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14685

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