Abstract
BackgroundThe 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 FindingsIn 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/SignificanceOur current study thus suggests that Nanos3-3′UTR has an essential role in translational control in the mouse embryo.
Highlights
The manner in which genes are regulated to produce the correct combination of proteins for every cell type remains a fundamental question in biology
By applying a transgenic mouse strategy, we show that the translation of NANOS3 in somatic cells is suppressed via an mRNA destabilizing mechanism mediated by the Nanos3-39UTR
To elucidate whether the Nanos3-39UTR is involved in NANOS3 expression in mouse, we generated two BAC transgenic mouse lines; BAC-Nanos3-mRFP(Nos3-39UTR) containing the endogenous Nanos3-39UTR (Fig. 1A and E), and BAC-Nanos3-mRFP(BghpA) harboring an exogenous 39UTR, Bovine growth hormone poly(A) signal (BghpA; Fig. 1B)
Summary
The manner in which genes are regulated to produce the correct combination of proteins for every cell type remains a fundamental question in biology. It is becoming clear that post-transcriptional regulation mediated via a 39 untranslated region (UTR) plays key roles in the control of mRNA stability and/or translation. During germ cell specification in Drosophila, maternal nanos mRNA becomes localized in the germ plasm in the posterior part of the egg [12,13] This localization is inefficient, and translational repression is essential for the restricted production of Nanos protein in the posterior region. The regulation of gene expression via a 39 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. The regulatory mechanisms that restrict the expression of this gene in the germ cells is largely unknown at present
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