RNA promotes phase separation of glycolysis enzymes into yeast G bodies in hypoxia
RNA promotes phase separation of glycolysis enzymes into yeast G bodies in hypoxia
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DOI：
10.7554/elife.48480
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发表时间：
2020-04-16
期刊：
影响因子：
7.7
通讯作者：
Kim, John K.
中科院分区：
文献类型：
--
作者：
Fuller, Gregory G.;Han, Ting;Kim, John K.
在缺氧应激条件下，糖酵解酶组装成称为糖酵解（G）体的单个细胞质颗粒。酵母中G体的形成与葡萄糖消耗增加和细胞存活相关。然而，定义G体形成的物理性质和组织原则尚不清楚。我们证明，糖酵解酶是非典型的RNA结合蛋白，共享许多共同的mRNA底物，也是G体的组成部分。将非特异性内切核糖核酸酶靶向G体揭示了RNA使G体形成成核并保持其结构完整性。与生物发生的相分离机制一致，糖酵解酶向G体的募集依赖于多价同型和异型相互作用。此外，G体在体内融合，并且对1，6-己二醇很大程度上不敏感，与水凝胶样组合物一致。两者合计，我们的研究结果阐明了生物物理性质的G机构，并表明，RNA成核相分离的糖酵解机制在缺氧应激。
In hypoxic stress conditions, glycolysis enzymes assemble into singular cytoplasmic granules called glycolytic (G) bodies. G body formation in yeast correlates with increased glucose consumption and cell survival. However, the physical properties and organizing principles that define G body formation are unclear. We demonstrate that glycolysis enzymes are non canonical RNA binding proteins, sharing many common mRNA substrates that are also integral constituents of G bodies. Targeting nonspecific endoribonucleases to G bodies reveals that RNA nucleates G body formation and maintains its structural integrity. Consistent with a phase separation mechanism of biogenesis, recruitment of glycolysis enzymes to G bodies relies on multivalent homotypic and heterotypic interactions. Furthermore, G bodies fuse in vivo and are largely insensitive to 1,6-hexanediol, consistent with a hydrogel-like composition. Taken together, our results elucidate the biophysical nature of G bodies and demonstrate that RNA nucleates phase separation of the glycolysis machinery in response to hypoxic stress.