MicroRNA filters Hox temporal transcription noise to confer boundary formation in the spinal cord.
MicroRNA filters Hox temporal transcription noise to confer boundary formation in the spinal cord.
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DOI：
10.1038/ncomms14685
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发表时间：
2017-03-24
影响因子：
16.6
通讯作者：
Chen JA
中科院分区：
文献类型：
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作者：
Li CJ;Hong T;Tung YT;Yen YP;Hsu HC;Lu YL;Chang M;Nie Q;Chen JA
神经管的初始喙尾图案导致Hox基因的差异表达，其有助于运动神经元（MN）亚型身份的规范。虽然一些3′ Hox mRNA在祖细胞中以嘈杂的方式表达，但这些Hox蛋白在祖细胞中不表达，并且仅在有丝分裂后的MN中可检测到。MicroRNA生物合成障碍导致过早表达，并在蛋白质水平传播Hoxa 5的噪音，导致Hoxa 5-Hoxc 8边界不精确。在这里，我们发现，使用计算机模拟，两个前馈Hox-miRNA环占早熟和嘈杂的Hoxa 5表达，以及一个不明确的边界表型在Dicer突变体。最后，我们确定了米尔-27作为一个主要的调节协调的时间延迟和Hox蛋白表达的空间边界。我们的研究结果提供了一种新的反式Hox-miRNA电路过滤转录噪音和控制蛋白质表达的时间，以赋予强大的个人MN身份。在脊髓中，一些Hox基因在祖细胞中转录，而其蛋白仅在分化的有丝分裂后运动神经元中检测到。在这里，作者表明，miRNA（特别是mir-27）调节运动神经元中的转录后Hoxa 5表达。
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. In the spinal cord, some Hox genes are transcribed in progenitors while their proteins are only detected in differentiating postmitotic motor neurons. Here, the authors show that miRNAs (specifically mir-27) regulate post-transcriptional Hoxa5 expression in motor neurons.