Saltel Frédéric, Giese Alban, Azzi Lamia, Elatmani Habiba, Costet Pierre, Ezzoukhry Zakaria, Dugot-Senant Nathalie, Miquerol Lucile, Boussadia Oréda, Wodrich Harald, Dubus Pierre, Jacquemin-Sablon Hélène
INSERM UMR1053 Bordeaux Research In Translational Oncology, BaRITOn, F-33000 Bordeaux, France
University of Bordeaux, F-33000 Bordeaux, France.
J Cell Sci. 2017 May 15;130(10):1796-1808. doi: 10.1242/jcs.198697. Epub 2017 Apr 6.
Unr (officially known as CSDE1) is a cytoplasmic RNA-binding protein with roles in the regulation of mRNA stability and translation. In this study, we identified a novel function for Unr, which acts as a positive regulator of placental development. Unr expression studies in the developing placenta revealed the presence of Unr-rich foci that are apparently located in the nuclei of trophoblast giant cells (TGCs). We determined that what we initially thought to be foci, were actually cross sections of a network of double-wall nuclear membrane invaginations that contain a cytoplasmic core related to the nucleoplasmic reticulum (NR). We named them, accordingly, Unr-NRs. Unr-NRs constitute a novel type of NR because they contain high levels of poly(A) RNA and translation factors, and are sites of active translation. In murine tissues, Unr-NRs are only found in two polyploid cell types, in TGCs and hepatocytes. , their formation is linked to stress and polyploidy because, in three cancer cell lines, cytotoxic drugs that are known to promote polyploidization induce their formation. Finally, we show that Unr is required for the formation of Unr-containing NRs because these structures are absent in null TGCs.
Unr(官方名称为CSDE1)是一种细胞质RNA结合蛋白,在调节mRNA稳定性和翻译方面发挥作用。在本研究中,我们确定了Unr的一种新功能,它作为胎盘发育的正向调节因子。对发育中的胎盘进行的Unr表达研究显示,存在富含Unr的病灶,这些病灶显然位于滋养层巨细胞(TGCs)的细胞核中。我们确定,我们最初认为是病灶的结构,实际上是双壁核膜内陷网络的横截面,其中包含与核质网(NR)相关的细胞质核心。因此,我们将它们命名为Unr-NRs。Unr-NRs构成了一种新型的NR,因为它们含有高水平的多聚腺苷酸(poly(A))RNA和翻译因子,并且是活跃翻译的场所。在小鼠组织中,Unr-NRs仅在两种多倍体细胞类型中发现,即TGCs和肝细胞。此外,它们的形成与应激和多倍体有关,因为在三种癌细胞系中,已知能促进多倍体化的细胞毒性药物会诱导它们的形成。最后,我们表明Unr是含Unr的NRs形成所必需的,因为在缺失Unr的TGCs中不存在这些结构。