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游走于线间:神经元内及神经元外定向 mRNA 运输和定位的机制。

Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond.

机构信息

Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.

UK Dementia Research Institute, University College London, London, WC1E 6BT, UK.

出版信息

Cell Mol Life Sci. 2021 Mar;78(6):2665-2681. doi: 10.1007/s00018-020-03724-3. Epub 2020 Dec 20.

Abstract

Messenger RNA (mRNA) localisation enables a high degree of spatiotemporal control on protein synthesis, which contributes to establishing the asymmetric protein distribution required to set up and maintain cellular polarity. As such, a tight control of mRNA localisation is essential for many biological processes during development and in adulthood, such as body axes determination in Drosophila melanogaster and synaptic plasticity in neurons. The mechanisms controlling how mRNAs are localised, including diffusion and entrapment, local degradation and directed active transport, are largely conserved across evolution and have been under investigation for decades in different biological models. In this review, we will discuss the standing of the field regarding directional mRNA transport in light of the recent discovery that RNA can hitchhike on cytoplasmic organelles, such as endolysosomes, and the impact of these transport modalities on our understanding of neuronal function during development, adulthood and in neurodegeneration.

摘要

信使 RNA(mRNA)定位使蛋白质合成具有高度的时空控制能力,有助于建立建立和维持细胞极性所需的不对称蛋白质分布。因此,mRNA 定位的严格控制对于发育和成年期的许多生物学过程至关重要,例如黑腹果蝇的体轴确定和神经元的突触可塑性。控制 mRNA 定位的机制,包括扩散和捕获、局部降解和定向主动运输,在进化过程中基本保守,并在不同的生物模型中进行了数十年的研究。在这篇综述中,我们将根据最近的发现讨论该领域在定向 mRNA 运输方面的地位,即 RNA 可以搭乘细胞质细胞器(如内溶酶体),以及这些运输方式对我们理解发育、成年和神经退行性变期间神经元功能的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/866a/11072864/e0f64c828033/18_2020_3724_Fig1_HTML.jpg

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