Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Cell and Developmental Biology and Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
G3 (Bethesda). 2022 Aug 25;12(9). doi: 10.1093/g3journal/jkac159.
Following fertilization, the unified germ cells rapidly transition to a totipotent embryo. Maternally deposited mRNAs encode the proteins necessary for this reprogramming as the zygotic genome remains transcriptionally quiescent during the initial stages of development. The transcription factors required to activate the zygotic genome are among these maternally deposited mRNAs and are robustly translated following fertilization. In Drosophila, the mRNA encoding Zelda, the major activator of the zygotic genome, is not translated until 1 h after fertilization. Here we demonstrate that zelda translation is repressed in the early embryo by the TRIM-NHL protein Brain tumor (BRAT). BRAT also regulates Zelda levels in the larval neuroblast lineage. In the embryo, BRAT-mediated translational repression is regulated by the Pan Gu kinase, which is triggered by egg activation. The Pan Gu kinase phosphorylates translational regulators, suggesting that Pan Gu kinase activity alleviates translational repression of zelda by BRAT and coupling translation of zelda with that of other regulators of early embryonic development. Using the premature translation of zelda in embryos lacking BRAT activity, we showed that early translation of a zygotic genome activator is not sufficient to drive precocious gene expression. Instead, Zelda-target genes showed increased expression at the time they are normally activated. We propose that transition through early development requires the integration of multiple processes, including the slowing of the nuclear division cycle and activation of the zygotic genome. These processes are coordinately controlled by Pan Gu kinase-mediated regulation of translation.
受精后，统一的生殖细胞迅速转变为全能胚胎。母体沉积的 mRNA 编码了重新编程所必需的蛋白质，因为合子基因组在发育的初始阶段保持转录静止。激活合子基因组所需的转录因子是这些母体沉积的 mRNA 之一，在受精后会被强烈翻译。在果蝇中，编码 Zelda 的 mRNA 是合子基因组的主要激活因子，直到受精后 1 小时才开始翻译。在这里，我们证明 Zelda 翻译在早期胚胎中被 TRIM-NHL 蛋白 Brain tumor (BRAT) 抑制。BRAT 还调节幼虫神经母细胞谱系中的 Zelda 水平。在胚胎中，BRAT 介导的翻译抑制受 Pan Gu 激酶调节，该激酶由卵子激活触发。Pan Gu 激酶磷酸化翻译调节因子，表明 Pan Gu 激酶活性缓解了 BRAT 对 zelda 的翻译抑制，并将 zelda 的翻译与早期胚胎发育的其他调节因子的翻译联系起来。使用缺乏 BRAT 活性的胚胎中 zelda 的过早翻译，我们表明，早期翻译的合子基因组激活因子不足以驱动过早的基因表达。相反，Zelda 靶基因在正常激活时的表达增加。我们提出，通过早期发育需要多个过程的整合，包括核分裂周期的减缓和合子基因组的激活。这些过程通过 Pan Gu 激酶介导的翻译调节得到协调控制。
