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神经元突起包含核糖体生物发生后期步骤的关键组成部分。

Neuronal processes contain the essential components for the late steps of ribosome biogenesis.

作者信息

Fusco Claudia M, Staab Anja, Bourke Ashley M, Tushev Georgi, Desch Kristina, Lins Erico Moreto, Ciirdaeva Elena, Tom Dieck Susanne, Kaltenschnee Nina, Heckel Alexander, Langer Julian D, Schuman Erin M

机构信息

Department of Synaptic Plasticity, Max Planck Institute for Brain Research, Frankfurt 60438, Germany.

Institute for Organic Chemistry and Chemical Biology, Goethe-University Frankfurt, Frankfurt 60438, Germany.

出版信息

Proc Natl Acad Sci U S A. 2025 Aug 5;122(31):e2502424122. doi: 10.1073/pnas.2502424122. Epub 2025 Jul 31.

DOI:10.1073/pnas.2502424122
PMID:40743395
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12337303/
Abstract

Neurons rely on spatial and temporal control of protein synthesis to respond rapidly and locally to external stimuli, a process facilitated by the dynamic localization and modification of ribosomes. While previous research has shown that neuronal activity can regulate ribosome localization and modify translation rates, little is known about ribosomal assembly within neuronal processes. Here, we investigated the potential for local ribosome maturation in rat neurons using proteomics, RNA sequencing, and imaging methods. We detected an abundance of ribosome biogenesis factors in distal neuronal compartments, particularly those associated with the late stages of ribosome assembly. Moreover, we detected cytosolic pre-ribosomal RNA species in dendrites, as well as the enzymes necessary for their processing, suggesting that local ribosome maturation can occur far from the nucleus. These findings challenge conventional models that confine ribosome biogenesis to nuclear and perinuclear regions and suggest that neurons may fine-tune local protein synthesis by regulating ribosome assembly near synaptic sites. This mechanism may enable rapid modulation of the translational capacity in response to physiological changes, regulating synaptic plasticity and local protein synthesis in neurons.

摘要

神经元依靠蛋白质合成的空间和时间控制来快速、局部地响应外部刺激,这一过程由核糖体的动态定位和修饰所促进。虽然先前的研究表明神经元活动可以调节核糖体定位并改变翻译速率,但对于神经元突起内的核糖体组装知之甚少。在这里,我们使用蛋白质组学、RNA测序和成像方法研究了大鼠神经元中局部核糖体成熟的可能性。我们在神经元远端区室中检测到大量核糖体生物发生因子,特别是那些与核糖体组装后期相关的因子。此外,我们在树突中检测到胞质前核糖体RNA种类,以及加工它们所需的酶,这表明局部核糖体成熟可以在远离细胞核的地方发生。这些发现挑战了将核糖体生物发生限制在细胞核和核周区域的传统模型,并表明神经元可能通过调节突触部位附近的核糖体组装来微调局部蛋白质合成。这种机制可能使翻译能力能够快速响应生理变化进行调节,从而调节神经元中的突触可塑性和局部蛋白质合成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/da3cbc1cdd8b/pnas.2502424122fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/56ef89a0f407/pnas.2502424122fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/f33c7fb3f940/pnas.2502424122fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/fef17b263ce1/pnas.2502424122fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/aef32da62315/pnas.2502424122fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/2f680cff5fef/pnas.2502424122fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/da3cbc1cdd8b/pnas.2502424122fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/56ef89a0f407/pnas.2502424122fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/f33c7fb3f940/pnas.2502424122fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/fef17b263ce1/pnas.2502424122fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/aef32da62315/pnas.2502424122fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/2f680cff5fef/pnas.2502424122fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e9/12337303/da3cbc1cdd8b/pnas.2502424122fig06.jpg

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RNA granules in neuronal plasticity and disease.神经元可塑性和疾病中的 RNA 颗粒。
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Chaperone-directed ribosome repair after oxidative damage.伴侣蛋白指导的核糖体氧化损伤后修复。
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Ribosome biogenesis factors-from names to functions.核糖体生物发生因子——从名字到功能。
EMBO J. 2023 Apr 3;42(7):e112699. doi: 10.15252/embj.2022112699. Epub 2023 Feb 10.
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De-centralizing the Central Dogma: mRNA translation in space and time.去中心化的中心法则:mRNA 在空间和时间上的翻译。
Mol Cell. 2023 Feb 2;83(3):452-468. doi: 10.1016/j.molcel.2022.12.030. Epub 2023 Jan 19.
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Excess ribosomal protein production unbalances translation in a model of Fragile X Syndrome.核糖体蛋白过量产生会使脆性 X 综合征模型中的翻译失衡。
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