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凝聚物作为翻译中心来协调多核细胞的生长。

Condensates act as translation hubs to coordinate multinucleate cell growth.

作者信息

Geisterfer Zachary M, Jalihal Ameya P, Cole Sierra J, Gladfelter Amy S

机构信息

Department of Cell Biology, Duke University, Durham, NC 27710.

Department of Biochemistry and Biophysics, UNC Chapel Hill, NC 27517.

出版信息

bioRxiv. 2024 Dec 17:2024.12.12.628219. doi: 10.1101/2024.12.12.628219.

DOI:10.1101/2024.12.12.628219
PMID:39763723
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11702524/
Abstract

Coordination between growth and division is a fundamental feature of cells. In many syncytia, cell growth must couple with multiple nuclear divisions in one cytoplasm. In the fungus, , cell-cycle progression and hyphal elongation require condensates formed by the protein Whi3 in complex with distinct mRNA species. We hypothesized the condensates may act through local translation regulation and find that Whi3 target mRNAs show distinct spatial biases in translation in vivo. Whi3-RNA condensates can both promote and repress RNA translation in an RNA- and condensate size-dependent manner in vitro. Interestingly, we observe a sub-condensate enrichment of translation that is tunable by RNA valency and protein phospho-state. Together, these data suggest that Whi3 condensates generate a continuum of translation states, resulting in asynchronous nuclear divisions coordinated with growth. This local regulation requires a minimal complement of molecular components at the nano scale to support global coordination at the cell scale.

摘要

生长与分裂之间的协调是细胞的一个基本特征。在许多合胞体中,细胞生长必须与一个细胞质中的多个核分裂相耦合。在真菌中,细胞周期进程和菌丝伸长需要由蛋白质Whi3与不同的mRNA种类形成的凝聚物。我们推测这些凝聚物可能通过局部翻译调控发挥作用,并发现Whi3靶标mRNA在体内翻译中表现出不同的空间偏向性。Whi3-RNA凝聚物在体外能以RNA和凝聚物大小依赖的方式促进和抑制RNA翻译。有趣的是,我们观察到翻译的亚凝聚物富集可由RNA价态和蛋白质磷酸化状态调节。总之,这些数据表明Whi3凝聚物产生了一个连续的翻译状态,导致与生长协调的异步核分裂。这种局部调控需要纳米尺度上最少的分子成分补充,以支持细胞尺度上的全局协调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/9cb5b3e41417/nihpp-2024.12.12.628219v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/9105c91beca3/nihpp-2024.12.12.628219v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/09e7283d6bd2/nihpp-2024.12.12.628219v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/477570c1ef2d/nihpp-2024.12.12.628219v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/45e8a3fdced1/nihpp-2024.12.12.628219v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/79124b824b9c/nihpp-2024.12.12.628219v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/3faf807d724f/nihpp-2024.12.12.628219v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/9cb5b3e41417/nihpp-2024.12.12.628219v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/9105c91beca3/nihpp-2024.12.12.628219v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/09e7283d6bd2/nihpp-2024.12.12.628219v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/477570c1ef2d/nihpp-2024.12.12.628219v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/45e8a3fdced1/nihpp-2024.12.12.628219v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/79124b824b9c/nihpp-2024.12.12.628219v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/3faf807d724f/nihpp-2024.12.12.628219v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d892/11702524/9cb5b3e41417/nihpp-2024.12.12.628219v1-f0007.jpg

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本文引用的文献

1
Spatial organization of translation and translational repression in two phases of germ granules.生殖泡中翻译和翻译抑制的空间组织分为两个阶段。
Nat Commun. 2024 Sep 13;15(1):8020. doi: 10.1038/s41467-024-52346-x.
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Biomolecular condensates regulate cellular electrochemical equilibria.生物分子凝聚物调节细胞的电化学平衡。
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Biomolecular condensates as stress sensors and modulators of bacterial signaling.生物分子凝聚物作为细菌信号转导的应激传感器和调节剂。
PLoS Pathog. 2024 Aug 15;20(8):e1012413. doi: 10.1371/journal.ppat.1012413. eCollection 2024 Aug.
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Multi-condensate state as a functional strategy to optimize the cell signaling output.多凝聚态作为一种优化细胞信号输出的功能策略。
Nat Commun. 2024 Jul 25;15(1):6268. doi: 10.1038/s41467-024-50489-5.
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Direct observation of translational activation by a ribonucleoprotein granule.核糖核蛋白颗粒介导的翻译激活的直接观察。
Nat Cell Biol. 2024 Aug;26(8):1322-1335. doi: 10.1038/s41556-024-01452-5. Epub 2024 Jul 4.
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Local environment in biomolecular condensates modulates enzymatic activity across length scales.生物分子凝聚物中的局部环境可在不同长度尺度上调节酶的活性。
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DDX6 modulates P-body and stress granule assembly, composition, and docking.DDX6 调节 P 体和应激颗粒的组装、组成和对接。
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Macromolecular condensation organizes nucleolar sub-phases to set up a pH gradient.大分子凝聚将核仁亚相组织起来,形成 pH 梯度。
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Spatially resolved single-cell translatomics at molecular resolution.分子分辨率下的空间分辨单细胞转导组学。
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