Department of Biological Sciences, Hunter College, City University of New York, New York, NY, USA.
Program in Molecular, Cellular, and Developmental Biology, the Graduate Center, City University of New York, New York, NY, USA.
RNA Biol. 2023 Jan;20(1):573-587. doi: 10.1080/15476286.2023.2242650.
Study of the timing and location for mRNA translation across model systems has begun to shed light on molecular events fundamental to such processes as intercellular communication, morphogenesis, and body pattern formation. In , the posterior mRNA determinant, , is transcribed maternally but translated only when properly localized at the oocyte's posterior cortex. Two effector proteins, Bruno1 and Cup, mediate steps of mRNA regulation. The current model in the field identifies Bruno1 as necessary for Cup's recruitment to mRNA and indispensable for 's translational repression. We now report that this Bruno1-Cup interaction leads to precise mRNA regulation during early oogenesis and, importantly, the two proteins mutually influence each other's mRNA expression and protein distribution in the egg chamber. We show that these factors stably associate with mRNA . Cup associates with mRNA without Bruno1, while surprisingly Bruno1's stable association with mRNA depends on Cup. We demonstrate that the essential factor for mRNA repression in early oogenesis is Cup, not Bruno1. Furthermore, we find that Cup is a key P-body component that maintains functional P-body morphology during oogenesis and is necessary for mRNA's association with P-bodies. Therefore, Cup drives the translational repression and stability of mRNA. These experimental results point to a regulatory feedback loop between Bruno 1 and Cup in early oogenesis that appears crucial for mRNA to reach the posterior pole and its expression in the egg chamber for accurate embryo development.
对模型系统中 mRNA 翻译的时间和位置的研究开始揭示出一些对细胞间通讯、形态发生和身体模式形成等过程至关重要的分子事件。在这项研究中,后 mRNA 决定簇 由母体转录,但只有在正确定位于卵母细胞的后皮质时才翻译。两种效应蛋白 Bruno1 和 Cup 介导 mRNA 调节的步骤。该领域目前的模型将 Bruno1 确定为 Cup 招募到 mRNA 所必需的,并且是 mRNA 翻译抑制所必需的。我们现在报告说,这种 Bruno1-Cup 相互作用导致了早期卵母细胞中 mRNA 的精确调节,重要的是,这两种蛋白质相互影响彼此在卵室中的 mRNA 表达和蛋白分布。我们表明这些因子与 mRNA 稳定地结合。没有 Bruno1 时 Cup 与 mRNA 结合,而令人惊讶的是 Bruno1 与 mRNA 的稳定结合依赖于 Cup。我们证明在早期卵母细胞中抑制 mRNA 的必需因子是 Cup,而不是 Bruno1。此外,我们发现 Cup 是 P 体的关键组成部分,它在卵母细胞发生过程中维持功能性 P 体形态,并使 mRNA 与 P 体结合。因此,Cup 驱动 mRNA 的翻译抑制和稳定性。这些实验结果表明,在早期卵母细胞中 Bruno1 和 Cup 之间存在一个调节反馈回路,这对于 mRNA 到达后极并在卵室中表达以实现胚胎发育的准确性似乎至关重要。