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平等结合伴侣动力蛋白轻链和双尾蛋白 D 依次作用将 mRNA 连接到动力蛋白上。

The Egalitarian binding partners Dynein light chain and Bicaudal-D act sequentially to link mRNA to the Dynein motor.

机构信息

Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, 1459 Laney Walker Blvd, Augusta, GA 30912, USA.

Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, 1459 Laney Walker Blvd, Augusta, GA 30912, USA

出版信息

Development. 2019 Aug 9;146(15):dev176529. doi: 10.1242/dev.176529.

Abstract

A conserved mechanism of polarity establishment is the localization of mRNA to specific cellular regions. Although it is clear that many mRNAs are transported along microtubules, much less is known about the mechanism by which these mRNAs are linked to microtubule motors. The RNA binding protein Egalitarian (Egl) is necessary for localization of several mRNAs in oocytes and embryos. Egl also interacts with Dynein light chain (Dlc) and Bicaudal-D (BicD). The role of Dlc and BicD in mRNA localization has remained elusive. Both proteins are required for oocyte specification, as is Egl. Null alleles in these genes result in an oogenesis block. In this report, we used an shRNA-depletion strategy to overcome the oogenesis block. Our findings reveal that the primary function of Dlc is to promote Egl dimerization. Loss of dimerization compromises the ability of Egl to bind RNA. Consequently, Egl is not bound to cargo, and is not able to efficiently associate with BicD and the Dynein motor. Our results therefore identify the key molecular steps required for assembling a localization-competent mRNP.

摘要

一种保守的极性建立机制是将 mRNA 定位到特定的细胞区域。虽然许多 mRNA 显然是沿着微管运输的,但对于这些 mRNA 与微管马达连接的机制知之甚少。RNA 结合蛋白平等主义者(Egl)对于卵母细胞和胚胎中几种 mRNA 的定位是必需的。Egl 还与动力蛋白轻链(Dlc)和双尾蛋白(BicD)相互作用。Dlc 和 BicD 在 mRNA 定位中的作用仍然难以捉摸。这两种蛋白质对于卵母细胞的特化都是必需的,Egl 也是如此。这些基因的 null 等位基因导致卵母细胞发生阻断。在本报告中,我们使用 shRNA 耗竭策略来克服卵母细胞阻断。我们的研究结果表明,Dlc 的主要功能是促进 Egl 二聚化。二聚化的丧失损害了 Egl 结合 RNA 的能力。因此,Egl 不能与货物结合,也不能有效地与 BicD 和动力蛋白结合。因此,我们的结果确定了组装具有定位能力的 mRNP 所需的关键分子步骤。

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