Fujimuro Takeshi, Matsui Takaaki, Nitanda Yasuhide, Matta Tatsuro, Sakumura Yuichi, Saito Michiko, Kohno Kenji, Nakahata Yasukazu, Bessho Yasumasa
Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
1] Biological Systems Design Laboratory, School of Information Science and Technology, Aichi Prefectural University, Nagakute, Aichi 480-1198, Japan [2] Laboratory of Neuronal Cell Morphogenesis, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.
Sci Rep. 2014 Sep 24;4:6462. doi: 10.1038/srep06462.
A set of genes in the posterior end of developing mouse embryos shows oscillatory expression, thereby regulating periodic somite segmentation. Although the mechanism for generating oscillation has extensively been clarified, what regulates the oscillation period is still unclear. We attempted to elongate the oscillation period by increasing the time to transcribe Hes7 in this research. We generated knock-in mice, in which a large intron was inserted into Hes7 3'UTR. The exogenous intron was unexpectedly not properly spliced out and the transcripts were prematurely terminated. Consequently, Hes7 mRNA lost its 3'UTR, thereby reducing the amount of Hes7 protein. Oscillation was damped in the knock-in embryos and periodic somite segmentation does not occur properly. Thus, we demonstrated that Hes7 3'UTR is essential to accumulate adequate amounts of Hes7 protein for the somite segmentation clock that orchestrates periodic somite formation.
在发育中的小鼠胚胎后端，一组基因呈现振荡表达，从而调节周期性体节分割。尽管产生振荡的机制已得到广泛阐明，但调节振荡周期的因素仍不清楚。在本研究中，我们试图通过增加Hes7转录时间来延长振荡周期。我们构建了敲入小鼠，其中一个大的内含子被插入到Hes7的3'UTR中。意外的是，外源内含子没有被正确剪接出来，转录本提前终止。结果，Hes7 mRNA失去了其3'UTR，从而减少了Hes7蛋白的量。在敲入胚胎中振荡受到抑制，周期性体节分割不能正常发生。因此，我们证明了Hes7的3'UTR对于积累足够量的Hes7蛋白以维持协调周期性体节形成的体节分割时钟至关重要。
