Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
PLoS Genet. 2012 May;8(5):e1002742. doi: 10.1371/journal.pgen.1002742. Epub 2012 May 31.
Translational repression is often accompanied by mRNA degradation. In contrast, many mRNAs in germ cells and neurons are "stored" in the cytoplasm in a repressed but stable form. Unlike repression, the stabilization of these mRNAs is surprisingly little understood. A key player in Caenorhabditis elegans germ cell development is the STAR domain protein GLD-1. By genome-wide analysis of mRNA regulation in the germ line, we observed that GLD-1 has a widespread role in repressing translation but, importantly, also in stabilizing a sub-population of its mRNA targets. Additionally, these mRNAs appear to be stabilized by the DDX6-like RNA helicase CGH-1, which is a conserved component of germ granules and processing bodies. Because many GLD-1 and CGH-1 stabilized mRNAs encode factors important for the oocyte-to-embryo transition (OET), our findings suggest that the regulation by GLD-1 and CGH-1 serves two purposes. Firstly, GLD-1-dependent repression prevents precocious translation of OET-promoting mRNAs. Secondly, GLD-1- and CGH-1-dependent stabilization ensures that these mRNAs are sufficiently abundant for robust translation when activated during OET. In the absence of this protective mechanism, the accumulation of OET-promoting mRNAs, and consequently the oocyte-to-embryo transition, might be compromised.
翻译抑制通常伴随着 mRNA 的降解。相比之下,生殖细胞和神经元中的许多 mRNA 以被抑制但稳定的形式“储存”在细胞质中。与抑制不同,这些 mRNA 的稳定机制令人惊讶地知之甚少。线虫生殖细胞发育中的一个关键蛋白是 STAR 结构域蛋白 GLD-1。通过对生殖系中 mRNA 调控的全基因组分析,我们观察到 GLD-1 在广泛抑制翻译方面发挥作用,但重要的是,它也在稳定其 mRNA 靶标中的一个亚群方面发挥作用。此外,这些 mRNA 似乎被 DDX6 样 RNA 解旋酶 CGH-1 稳定,CGH-1 是生殖颗粒和处理体的保守成分。由于许多 GLD-1 和 CGH-1 稳定的 mRNA 编码对卵母细胞到胚胎过渡 (OET) 很重要的因素,我们的发现表明 GLD-1 和 CGH-1 的调节有两个目的。首先,GLD-1 依赖性抑制可防止 OET 促进的 mRNA 过早翻译。其次,GLD-1 和 CGH-1 依赖性稳定确保了这些 mRNA 在 OET 期间被激活时,其翻译充分丰富。如果没有这种保护机制,OET 促进的 mRNA 的积累,以及随后的卵母细胞到胚胎的过渡,可能会受到影响。