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首页> 外文期刊>PLoS Genetics >Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation
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Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation

机译:Makorin 1通过缓解Bruno1介导的<斜视> oskar 翻译来控制胚胎图案

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Makorins are evolutionary conserved proteins that contain C _(3)H-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.
机译:Makorins是进化保守蛋白质,其含有C _(3)H型锌指模块和环E3泛素连接酶结构域。在果蝇中,母体Makorin 1(MKRN1)已与胚胎图案连接,但该机制保持未解决。在这里,我们表明MKRN1对于轴规格和极柱组件至关重要,通过oskar(OSK)的翻译激活。我们证明MKRN1与聚(A)结合蛋白(PABP)相互作用,并且在与富含富份序列相邻的区域中特别结合OSK 3'UTR。使用果蝇S2R +培养细胞,我们表明该结合位点与调节OSK翻译的Bruno1(BRU1)响应元件(BRES)重叠。在MKRN1耗尽时,我们观察转化抑制剂BRU1与OSK mRNA的增加,表明两种蛋白质都竞争OSK结合。始终如一地,在MKRN1女性中减少BRU1剂量部分抵押卵巢中的活力和OSK蛋白质水平。我们得出结论,MKRN1通过专门激活OSK翻译来控制胚胎图案化和生殖细胞形成,最有可能通过与BRU1竞争结合OSK 3'UTR。

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