oskarRNP颗粒的液固相变对果蝇胚胎发育至关重要
2022-03-27   阅读:528   来源:细胞

欧洲分子生物学实验室Anne Ephrussi、Julia Mahamid研究组合作取得一项新突破。他们研究揭示了在果蝇胚胎发育过程中,oskar核糖核蛋白 (RNP)颗粒的液-固相变对其功能至关重要。该研究于2022年3月23日发表于国际一流学术期刊《细胞》杂志上。

他们表明,卵母细胞中的 oskar RNP 颗粒是具有固体状物理特性的凝聚物。使用纯化的 oskar RNA 以及支架蛋白 Bruno 和 Hrp48,他们在体外证实 oskar 颗粒经历了液体到固体的相变。虽然液相允许 RNA 掺入,但固相阻止了额外 RNA 的掺入,同时允许客户蛋白质的 RNA 依赖性分区。支架颗粒蛋白的遗传修饰或将人类肉瘤融合 (FUS) 的内在无序区域束缚到 oskar mRNA 允许在体内调节颗粒材料特性。由此产生的类似液体的特性破坏了 oskar 的定位和翻译,对胚胎发育造成了严重后果。他们的研究反映了生理相变如何塑造 RNA 蛋白凝聚物以调节指导生殖细胞形成的母体 RNA 的定位和表达。

据悉,oskar RNP颗粒到卵母细胞后部的不对称定位对于果蝇胚胎中的腹部模式和生殖系形成至关重要。

附:英文原文

Title: Liquid-to-solid phase transition of oskar ribonucleoprotein granules is essential for their function in Drosophila embryonic development

Author: Mainak Bose, Marko Lampe, Julia Mahamid, Anne Ephrussi

Issue&Volume: 2022-03-23

Abstract: Asymmetric localization of oskar ribonucleoprotein (RNP) granules to the oocyte posterior is crucial for abdominal patterning and germline formation in the Drosophila embryo. We show that oskar RNP granules in the oocyte are condensates with solid-like physical properties. Using purified oskar RNA and scaffold proteins Bruno and Hrp48, we confirm in vitro that oskar granules undergo a liquid-to-solid phase transition. Whereas the liquid phase allows RNA incorporation, the solid phase precludes incorporation of additional RNA while allowing RNA-dependent partitioning of client proteins. Genetic modification of scaffold granule proteins or tethering the intrinsically disordered region of human fused in sarcoma (FUS) to oskar mRNA allowed modulation of granule material properties in vivo. The resulting liquid-like properties impaired oskar localization and translation with severe consequences on embryonic development. Our study reflects how physiological phase transitions shape RNA-protein condensates to regulate the localization and expression of a maternal RNA that instructs germline formation.

DOI: 10.1016/j.cell.2022.02.022

编辑:小柯机器人

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