Aguero Tristan, Jin Zhigang, Chorghade Sandip, Kalsotra Auinash, King Mary Lou, Yang Jing
Department of Cell Biology, University of Miami, Miami, FL 33136, USA.
Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, IL 61802, USA.
Development. 2017 Oct 15;144(20):3755-3765. doi: 10.1242/dev.152611. Epub 2017 Sep 4.
In the developing embryo, primordial germ cells (PGCs) represent the exclusive progenitors of the gametes, and their loss results in adult infertility. During early development, PGCs are exposed to numerous signals that specify somatic cell fates. To prevent somatic differentiation, PGCs must transiently silence their genome, an early developmental process that requires Nanos activity. However, it is unclear how Nanos translation is regulated in developing embryos. We report here that translation of after fertilization requires Dead-end 1 (Dnd1), a vertebrate-specific germline RNA-binding protein. We provide evidence that Dnd1 protein, expression of which is low in oocytes, but increases dramatically after fertilization, directly interacts with, and relieves the inhibitory function of eukaryotic initiation factor 3f, a repressive component in the 43S preinitiation complex. This work uncovers a novel translational regulatory mechanism that is fundamentally important for germline development.
在发育中的胚胎中,原始生殖细胞(PGCs)是配子的唯一祖细胞,它们的缺失会导致成年后不育。在早期发育过程中,PGCs会接触到许多决定体细胞命运的信号。为了防止体细胞分化,PGCs必须暂时沉默其基因组,这是一个早期发育过程,需要Nanos活性。然而,目前尚不清楚在发育中的胚胎中Nanos的翻译是如何受到调控的。我们在此报告,受精后Nanos的翻译需要Dead-end 1(Dnd1),一种脊椎动物特有的生殖系RNA结合蛋白。我们提供的证据表明,Dnd1蛋白在卵母细胞中的表达较低,但在受精后会显著增加,它直接与真核起始因子3f相互作用,并解除其抑制功能,真核起始因子3f是43S预起始复合物中的一种抑制成分。这项工作揭示了一种对生殖系发育至关重要的新型翻译调控机制。