Cup is essential for oskar mRNA translational repression during early Drosophila oogenesis.

Cup is essential for oskar mRNA translational repression during early Drosophila oogenesis.
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DOI:
10.1080/15476286.2023.2242650
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发表时间:
2023-01
期刊:
影响因子:
4.1
通讯作者:
Bratu, Diana P.
Bratu, Diana P.
中科院分区:
生物学3区
文献类型:
--
作者:
Bayer, Livia V.;Milano, Samantha;Formel, Stephen K.;Kaur, Harpreet;Ravichandran, Rishi;Cambeiro, Juan A.;Slinko, Lizaveta;Catrina, Irina E.;Bratu, Diana P.

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对跨模型系统的mRNA翻译的时间和位置的研究已经开始揭示细胞间通信、形态发生和身体模式形成等过程的基本分子事件。在黑腹毛虫中,后面的mRNA决定因素Oskar是母系转录的,但只有在卵母细胞的后部皮质适当定位时才能翻译。两个效应蛋白,Bruno1和CUP,介导了Oskar mRNA的调节步骤。目前该领域的模型认为Bruno1是Cup招募到Oskar mRNA所必需的,也是Oskar翻译抑制所必需的。我们现在报道,这种Bruno1-CUP相互作用导致了早期卵子发生过程中Oskar mRNA的精确调控,而且,重要的是,这两种蛋白质相互影响对方的mRNA表达和卵室中的蛋白质分布。我们发现这些因子与体内的Oskar基因有稳定的关联。CUP与没有Bruno1的Oskar mRNA关联,而令人惊讶的是Bruno1的S与Oskar mRNA的稳定关联依赖于CUP。我们证明在卵子发生早期抑制Oskar基因的关键因子是cUP,而不是Bruno1。此外,我们还发现,在卵子发生过程中,Cup是维持功能P体形态的关键P体成分,也是Oskar mRNA与P体结合所必需的。因此,CUP驱动了Oskar mRNA的翻译抑制和稳定性。这些实验结果表明,在早期卵子发生中,Bruno 1和CUP之间存在一个调控反馈环,这似乎对Oskar mRNA到达后极及其在卵室中的表达对于准确的胚胎发育至关重要。
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 D. melanogaster, the posterior mRNA determinant, oskar, is transcribed maternally but translated only when properly localized at the oocyte’s posterior cortex. Two effector proteins, Bruno1 and Cup, mediate steps of oskar mRNA regulation. The current model in the field identifies Bruno1 as necessary for Cup’s recruitment to oskar mRNA and indispensable for oskar’s translational repression. We now report that this Bruno1-Cup interaction leads to precise oskar 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 oskar mRNA in vivo. Cup associates with oskar mRNA without Bruno1, while surprisingly Bruno1’s stable association with oskar mRNA depends on Cup. We demonstrate that the essential factor for oskar 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 oskar mRNA’s association with P-bodies. Therefore, Cup drives the translational repression and stability of oskar mRNA. These experimental results point to a regulatory feedback loop between Bruno 1 and Cup in early oogenesis that appears crucial for oskar mRNA to reach the posterior pole and its expression in the egg chamber for accurate embryo development.
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