Mir-125a-5p-mediated regulation of Lfng is essential for the avian segmentation clock.
Mir-125a-5p-mediated regulation of Lfng is essential for the avian segmentation clock.
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DOI：
10.1016/j.devcel.2013.01.024
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发表时间：
2013-03-11
影响因子：
11.8
通讯作者：
Cole, Susan E.
中科院分区：
文献类型：
--
作者：
Riley, Maurisa F.;Bochter, Matthew S.;Wahi, Kanu;Nuovo, Gerard J.;Cole, Susan E.
体节是脊椎动物中轴骨骼和骨骼肌的胚胎前体细胞，是脊椎动物节段性身体结构的基础。体细胞发生部分地由一个分段时钟控制，该时钟需要包括Lunatic fringe（Lfng）在内的基因的振荡表达。振荡基因必须在转录和转录后水平上受到严格的调控，才能发挥正常的生物钟功能。在这里，我们证明了microRNA介导的调节Lfng是必要的适当分割在鸡的体节发生。我们发现mir-125 a-5 p靶向Lfng 3′UTR中进化上保守的序列，并且阻止mir-125 a-5 p和Lfng转录本之间在体内的相互作用会导致异常分割并扰乱时钟活性。这提供了强有力的证据，证明miRNA在分割时钟中振荡基因的转录后调节中发挥作用。此外，这表明miRNA对靶基因的相对微妙的影响可以在对严格的转录后调控具有关键要求的发育情况中具有广泛的影响。
Somites are embryonic precursors of the axial skeleton and skeletal muscles, and establish the segmental vertebrate body plan. Somitogenesis is controlled in part by a segmentation clock that requires oscillatory expression of genes including Lunatic fringe (Lfng). Oscillatory genes must be tightly regulated both at the transcriptional and post-transcriptional levels for proper clock function. Here we demonstrate that microRNA-mediated regulation of Lfng is essential for proper segmentation during chick somitogenesis. We find that mir-125a-5p targets evolutionarily conserved sequences in the Lfng 3′UTR, and that preventing interactions between mir-125a-5p and Lfng transcripts in vivo causes abnormal segmentation and perturbs clock activity. This provides strong evidence that miRNAs function in the post-transcriptional regulation of oscillatory genes in the segmentation clock. Further, this demonstrates that the relatively subtle effects of miRNAs on target genes can have broad effects in developmental situations that have critical requirements for tight post-transcriptional regulation.
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