UBAP2L Forms Distinct Cores that Act in Nucleating Stress Granules Upstream of G3BP1
UBAP2L Forms Distinct Cores that Act in Nucleating Stress Granules Upstream of G3BP1
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DOI：
10.1016/j.cub.2019.12.020
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发表时间：
2020-02-24
期刊：
影响因子：
9.2
通讯作者：
Gotta, Monica
中科院分区：
文献类型：
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作者：
Cirillo, Luca;Cieren, Adeline;Gotta, Monica
应激颗粒（SG）是真核细胞在应激暴露后形成的无膜细胞器[1]（综述见[2-4]）。翻译抑制后，多核糖体解体释放48 S前起始复合物（PIC）。mRNA、PIC和其他蛋白质在SG核心中聚结[1，5-7]。SG核心招募动态壳，其性质由蛋白质和RNA之间的弱相互作用主导[8-10]。SG的结构和组装以及不同组件如何有助于其形成尚未完全了解。使用超分辨率和放大显微镜，我们发现SG组分UBAP 2L [11，12]和核心蛋白G3 BP 1 [5，11-13]占据SG内部的不同结构域。UBAP 2L显示核心蛋白的典型特性，表明不同组成的核心在同一颗粒内共存。与作为核心蛋白的作用一致，UBAP 2L在几种应激条件下是SG组装所需的。我们的反向遗传学和细胞生物学实验表明，UBAP 2L形成颗粒独立于G3 BP 1和2，但不干扰应激诱导的翻译抑制。我们提出了一个模型，其中UBAP 2L是一个必不可少的SG成核剂，其作用于G3 BP 1和2的上游，并促进G3 BP 1核心形成和SG组装和生长。
Stress granules (SGs) are membraneless organelles that form in eukaryotic cells after stress exposure [1] (reviewed in [2-4]). Following translation inhibition, polysome disassembly releases 48S preinitiation complexes (PICs). mRNA, PICs, and other proteins coalesce in SG cores [1, 5-7]. SG cores recruit a dynamic shell, whose properties are dominated by weak interactions between proteins and RNAs [8-10]. The structure and assembly of SGs and how different components contribute to their formation are not fully understood. Using super-resolution and expansion microscopy, we find that the SG component UBAP2L [11, 12] and the core protein G3BP1 [5, 11-13] occupy different domains inside SGs. UBAP2L displays typical properties of a core protein, indicating that cores of different compositions coexist inside the same granule. Consistent with a role as a core protein, UBAP2L is required for SG assembly in several stress conditions. Our reverse genetic and cell biology experiments suggest that UBAP2L forms granules independent of G3BP1 and 2 but does not interfere with stress-induced translational inhibition. We propose a model in which UBAP2L is an essential SG nucleator that acts upstream of G3BP1 and 2 and facilitates G3BP1 core formation and SG assembly and growth.