Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation
Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation
复制标题
DOI：
10.1371/journal.pgen.1008581
复制
发表时间：
2020-01-01
期刊：
影响因子：
4.5
通讯作者：
Lasko, Paul
中科院分区：
文献类型：
--
作者：
Dold, Annabelle;Han, Hong;Lasko, Paul
Makorins是进化上保守的蛋白质，含有C3H型锌指模块和RING E3泛素连接酶结构域。在果蝇中，母体Makorin 1（Mkrn 1）与胚胎模式有关，但机制尚未解决。在这里，我们表明，Mkrn1是必不可少的轴规范和极等离子体组装的翻译激活奥斯卡（osk）。我们证明Mkrn1与poly（A）结合蛋白（pAbp）相互作用，并特异性结合富含A序列附近区域的osk 3' UTR。使用果蝇S2R+培养的细胞，我们表明，这个结合位点与布鲁诺1（Bru 1）响应元件（BREs），调节osk翻译重叠。我们观察到增加协会的翻译抑制Bru 1与osk mRNA耗尽Mkrn1后，表明这两种蛋白质竞争osk结合。一致地，减少Bru 1剂量部分地挽救来自Mkrn 1雌性的卵巢中的活力和Osk蛋白水平。我们的结论是，Mkrn1控制胚胎图案和生殖细胞的形成，特别是通过激活osk翻译，最有可能通过竞争与Bru 1结合osk 3'UTR.Author summaryTo确保准确的发展果蝇胚胎，蛋白质和mRNA定位在特定的网站内的胚胎。其中许多因素是在母亲卵子发育过程中产生和定位的。一种对这个过程至关重要的蛋白质是Oskar（Osk），它位于后极。在osk mRNA的定位过程中，它的翻译被RNA结合蛋白Bruno 1（Bru 1）抑制，确保Osk蛋白不存在于它有害的后部之外。在后极，osk mRNA通过尚不清楚的机制被激活。在这项工作中，我们表明，保守的蛋白Makorin 1（Mkrn1）是一个新的因素参与翻译激活的osk。Mkrn1与osk mRNA特异性结合，与Bru 1的结合位点重叠，从而减轻Bru 1与osk的结合。此外，Mkrn1是由poly（A）结合蛋白（pAbp）稳定的，pAbp是一种翻译激活剂，可在一个Mkrn1结合位点附近结合osk mRNA。因此，我们的工作有助于回答该领域一个长期存在的问题，提供有关Mkrn1功能的见解，并更普遍地了解动物的胚胎模式。
Makorins are evolutionary conserved proteins that contain C3H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila, maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar (osk). We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds specifically to osk 3' UTR in a region adjacent to A-rich sequences. Using Drosophila S2R+ cultured cells we show that this binding site overlaps with a Bruno1 (Bru1) responsive element (BREs) that regulates osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation, most likely by competing with Bru1 to bind to osk 3' UTR.Author summaryTo ensure accurate development of the Drosophila embryo, proteins and mRNAs are positioned at specific sites within the embryo. Many of these factors are produced and localized during the development of the egg in the mother. One protein essential for this process that has been heavily studied is Oskar (Osk), which is positioned at the posterior pole. During the localization of osk mRNA, its translation is repressed by the RNA-binding protein Bruno1 (Bru1), ensuring that Osk protein is not present outside of the posterior where it is harmful. At the posterior pole, osk mRNA is activated through mechanisms that are not yet understood. In this work, we show that the conserved protein Makorin 1 (Mkrn1) is a novel factor involved in the translational activation of osk. Mkrn1 binds specifically to osk mRNA, overlapping with a binding site of Bru1, thus alleviating the association of Bru1 with osk. Moreover, Mkrn1 is stabilized by poly(A) binding protein (pAbp), a translational activator that binds osk mRNA in close proximity to one Mkrn1 binding site. Our work thus helps to answer a long-standing question in the field, providing insight about the function of Mkrn1 and more generally into embryonic patterning in animals.