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解析核孔复合物介导的 mRNA 出核转运的衔接和起始过程。

Unraveling docking and initiation of mRNA export through the nuclear pore complex.

机构信息

Department of Biology, Temple University, Philadelphia, Pennsylvania, USA.

出版信息

Bioessays. 2022 Aug;44(8):e2200027. doi: 10.1002/bies.202200027. Epub 2022 Jun 26.

DOI:10.1002/bies.202200027
PMID:35754154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9308666/
Abstract

The nuclear export of mRNA through the nuclear pore complex (NPC) is a process required for the healthy functioning of human cells, making it a critical area of research. However, the geometries of mRNA and the NPC are well below the diffraction limit of light microscopy, thereby presenting significant challenges in evaluating the discrete interactions and dynamics involved in mRNA nuclear export through the native NPC. Recent advances in biotechnology and single-molecule super-resolution light microscopy have enabled researchers to gain granular insight into the specific contributions made by discrete nucleoporins in the nuclear basket of the NPC to the export of mRNA. Specifically, by expanding upon the docking step facilitated by the protein TPR in the nuclear basket as well as identifying NUP153 as being the primary nuclear basket protein initiating export through the central channel of the NPC.

摘要

mRNA 通过核孔复合体(NPC)的核输出是人类细胞正常功能所必需的过程,因此成为了一个关键的研究领域。然而,mRNA 和 NPC 的几何形状远低于光显微镜的衍射极限,从而在评估通过天然 NPC 进行的 mRNA 核输出的离散相互作用和动力学方面带来了重大挑战。生物技术和单分子超分辨率荧光显微镜的最新进展使研究人员能够深入了解 NPC 核篮状结构中的离散核孔蛋白在 mRNA 核输出中所做出的具体贡献。具体来说,通过扩展核篮状结构中 TPR 蛋白所促进的对接步骤,并确定 NUP153 是通过 NPC 中央通道起始输出的主要核篮状结构蛋白。

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本文引用的文献

1
Distinct roles of nuclear basket proteins in directing the passage of mRNA through the nuclear pore.核篮蛋白在指导 mRNA 通过核孔的过程中发挥独特作用。
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37). doi: 10.1073/pnas.2015621118.
2
High-speed super-resolution imaging of rotationally symmetric structures using SPEED microscopy and 2D-to-3D transformation.利用 SPEED 显微镜和 2D-3D 转换技术实现旋转对称结构的高速超分辨率成像。
Nat Protoc. 2021 Jan;16(1):532-560. doi: 10.1038/s41596-020-00440-x. Epub 2020 Dec 14.
3
Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway.核孔蛋白TPR是TREX-2 mRNA输出途径的一个组成部分。
Nat Commun. 2020 Sep 11;11(1):4577. doi: 10.1038/s41467-020-18266-2.
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Structure and Function of the TREX-2 Complex.TREX-2复合体的结构与功能
Subcell Biochem. 2019;93:461-470. doi: 10.1007/978-3-030-28151-9_15.
5
Into the basket and beyond: the journey of mRNA through the nuclear pore complex.进入篮子并超越:mRNA 通过核孔复合体的旅程。
Biochem J. 2020 Jan 17;477(1):23-44. doi: 10.1042/BCJ20190132.
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Casting a Wider Net: Differentiating between Inner Nuclear Envelope and Outer Nuclear Envelope Transmembrane Proteins.广撒网:区分核内、核膜跨膜蛋白。
Int J Mol Sci. 2019 Oct 23;20(21):5248. doi: 10.3390/ijms20215248.
7
Mechanisms of nuclear mRNA export: A structural perspective.核 mRNA 输出的机制:结构视角。
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8
3D Tracking-Free Approach for Obtaining 3D Super-Resolution Information in Rotationally Symmetric Biostructures.3D 无追踪方法在旋转对称生物结构中获取 3D 超分辨率信息。
J Phys Chem B. 2019 Jun 20;123(24):5107-5120. doi: 10.1021/acs.jpcb.9b02979. Epub 2019 Jun 10.
9
Nuclear export of mRNA molecules studied by SPEED microscopy.通过 SPEED 显微镜研究 mRNA 分子的核输出。
Methods. 2019 Jan 15;153:46-62. doi: 10.1016/j.ymeth.2018.08.005. Epub 2018 Aug 18.
10
Integrative structure and functional anatomy of a nuclear pore complex.核孔复合体的综合结构和功能解剖。
Nature. 2018 Mar 22;555(7697):475-482. doi: 10.1038/nature26003. Epub 2018 Mar 14.