Friday Andrew J, Keiper Brett D
Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Biomed Res Int. 2015;2015:327963. doi: 10.1155/2015/327963. Epub 2015 Aug 19.
Ultimately, the production of new proteins in undetermined cells pushes them to new fates. Other proteins hold a stem cell in a mode of self-renewal. In germ cells, these decision-making proteins are produced largely from translational control of preexisting mRNAs. To date, all of the regulation has been attributed to RNA binding proteins (RBPs) that repress mRNAs in many models of germ cell development (Drosophila, mouse, C. elegans, and Xenopus). In this review, we focus on the selective, positive function of translation initiation factors eIF4E and eIF4G, which recruit mRNAs to ribosomes upon derepression. Evidence now shows that the two events are not separate but rather are coordinated through composite complexes of repressors and germ cell isoforms of eIF4 factors. Strikingly, the initiation factor isoforms are themselves mRNA selective. The mRNP complexes of translation factors and RBPs are built on specific populations of mRNAs to prime them for subsequent translation initiation. Simple rearrangement of the partners causes a dormant mRNP to become synthetically active in germ cells when and where they are required to support gametogenesis.
最终，未分化细胞中新型蛋白质的产生将它们推向新的命运。其他蛋白质则使干细胞维持自我更新模式。在生殖细胞中，这些决策蛋白很大程度上是通过对已有mRNA的翻译控制产生的。迄今为止，所有的调控都归因于RNA结合蛋白（RBPs），在许多生殖细胞发育模型（果蝇、小鼠、秀丽隐杆线虫和非洲爪蟾）中，这些蛋白会抑制mRNA。在本综述中，我们聚焦于翻译起始因子eIF4E和eIF4G的选择性正向功能，它们在去抑制后会将mRNA招募到核糖体上。现在有证据表明，这两个事件并非相互独立，而是通过阻遏物与eIF4因子的生殖细胞异构体的复合复合物进行协调。引人注目的是，起始因子异构体本身对mRNA具有选择性。翻译因子和RBPs的mRNP复合物基于特定的mRNA群体构建而成，使其为后续的翻译起始做好准备。伴侣的简单重排会使处于休眠状态的mRNP在生殖细胞中需要支持配子发生的时间和地点变得具有合成活性。
