Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan.
PLoS One. 2010 Feb 18;5(2):e9300. doi: 10.1371/journal.pone.0009300.
The regulation of gene expression via a 3' untranslated region (UTR) plays essential roles in the discrimination of the germ cell lineage from somatic cells during embryogenesis. This is fundamental to the continuation of a species. Mouse NANOS3 is an essential protein required for the germ cell maintenance and is specifically expressed in these cells. However, the regulatory mechanisms that restrict the expression of this gene in the germ cells is largely unknown at present.
METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we show that differences in the stability of Nanos3 mRNA between germ cells and somatic cells is brought about in a 3'UTR-dependent manner in mouse embryos. Although Nanos3 is transcribed in both cell lineages, it is efficiently translated only in the germ lineage. We also find that the translational suppression of NANOS3 in somatic cells is caused by a 3'UTR-mediated mRNA destabilizing mechanism. Surprisingly, even when under the control of the CAG promoter which induces strong ubiquitous transcription in both germ cells and somatic cells, the addition of the Nanos3-3'UTR sequence to the coding region of exogenous gene was effective in restricting protein expression in germ cells.
CONCLUSIONS/SIGNIFICANCE: Our current study thus suggests that Nanos3-3'UTR has an essential role in translational control in the mouse embryo.
通过 3'非翻译区(UTR)调节基因表达,在胚胎发生过程中对于从体细胞中区分生殖细胞谱系起着至关重要的作用。这对于物种的延续是基础。小鼠 NANOS3 是维持生殖细胞所必需的必需蛋白,并且特异性地在这些细胞中表达。然而,目前对于限制该基因在生殖细胞中表达的调控机制知之甚少。
方法/主要发现:在我们目前的研究中,我们表明,在小鼠胚胎中,生殖细胞和体细胞之间 Nanos3 mRNA 稳定性的差异是通过 3'UTR 依赖性方式产生的。尽管 Nanos3 在两个细胞谱系中均被转录,但仅在生殖谱系中有效地翻译。我们还发现,NANOS3 在体细胞中的翻译抑制是由 3'UTR 介导的 mRNA 不稳定机制引起的。令人惊讶的是,即使在外源基因的编码区受 CAG 启动子的控制,该启动子在生殖细胞和体细胞中均诱导强烈的普遍转录,添加 Nanos3-3'UTR 序列也能有效地限制生殖细胞中的蛋白表达。
结论/意义:因此,我们目前的研究表明,Nanos3-3'UTR 在小鼠胚胎中的翻译控制中起着重要作用。