Oulhen Nathalie, Wessel Gary M
Department of Molecular and Cell Biology and Biochemistry, Brown University, 185 Meeting St., Providence, RI 02912, USA.
Department of Molecular and Cell Biology and Biochemistry, Brown University, 185 Meeting St., Providence, RI 02912, USA.
Dev Biol. 2016 Oct 1;418(1):146-156. doi: 10.1016/j.ydbio.2016.07.007. Epub 2016 Jul 14.
Nanos is a translational regulator required for the survival and maintenance of primordial germ cells. In the sea urchin, Strongylocentrotus purpuratus (Sp), Nanos 2 mRNA is broadly transcribed but accumulates specifically in the small micromere (sMic) lineage, in part because of the 3'UTR element GNARLE leads to turnover in somatic cells but retention in the sMics. Here we found that the Nanos 2 protein is also selectively stabilized; it is initially translated throughout the embryo but turned over in the future somatic cells and retained only in the sMics, the future germ line in this animal. This differential stability of Nanos protein is dependent on the open reading frame (ORF), and is independent of the sumoylation and ubiquitylation pathways. Manipulation of the ORF indicates that 68 amino acids in the N terminus of the Nanos protein are essential for its stability in the sMics whereas a 45 amino acid element adjacent to the zinc fingers targets its degradation. Further, this regulation of Nanos protein is cell autonomous, following formation of the germ line. These results are paradigmatic for the unique presence of Nanos in the germ line by a combination of selective RNA retention, distinctive translational control mechanisms (Oulhen et al., 2013), and now also by defined Nanos protein stability.
Nanos是原始生殖细胞存活和维持所必需的一种翻译调节因子。在海胆紫球海胆（Sp）中，Nanos 2 mRNA广泛转录，但特异性地在小分裂球（sMic）谱系中积累，部分原因是3'UTR元件GNARLE导致其在体细胞中周转，但在小分裂球中保留。在这里，我们发现Nanos 2蛋白也被选择性地稳定；它最初在整个胚胎中翻译，但在未来的体细胞中周转，仅保留在小分裂球中，即该动物未来的生殖系。Nanos蛋白的这种差异稳定性取决于开放阅读框（ORF），并且独立于SUMO化和泛素化途径。对ORF的操作表明，Nanos蛋白N端的68个氨基酸对于其在小分裂球中的稳定性至关重要，而与锌指相邻的一个45个氨基酸的元件靶向其降解。此外，在生殖系形成后，Nanos蛋白的这种调节是细胞自主的。这些结果通过选择性RNA保留、独特的翻译控制机制（Oulhen等人，2013年）以及现在确定的Nanos蛋白稳定性的组合，成为生殖系中Nanos独特存在的范例。
