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一种相分离的SR蛋白重编程宿主前体mRNA剪接以增强疾病易感性。

A Phase-Separated SR Protein Reprograms Host Pre-mRNA Splicing to Enhance Disease Susceptibility.

作者信息

Yan Dong, Huang Jie, Tian Fengqi, Shu Haidong, Chen Han, Peng Qian, Wu Hongwei, Zhao Jianlong, Reddy Anireddy S N, Li Gang, Wang Yuanchao, Dong Suomeng

机构信息

State Key Laboratory of Agricultural and Forestry Biosecurity, College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, China.

The Plant Chemetics Laboratory, Department of Biology, University of Oxford, Oxford, OX1 3RB, UK.

出版信息

Adv Sci (Weinh). 2025 Jul;12(27):e2500072. doi: 10.1002/advs.202500072. Epub 2025 May 8.

DOI:10.1002/advs.202500072
PMID:40344631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12279203/
Abstract

Alternative splicing (AS) plays a vital role in the plant-microbe interaction. Modulating host precursor-mRNA AS is a key strategy employed by multiple pathogens to subvert plant immunity. However, the underlying mechanism by which the host splicing factor regulates plant immunity remains poorly understood. Here, a plant-conserved serine/arginine-rich (SR) RNA splicing factor, SR30, which negatively regulates tomato immunity against the infamous Phytophthora infestans (P. infestans) is identified. SR30 governs tomato mRNA AS at a genome-wide level and suppresses defense-related genes AS. During P. infestans infection, SR30 is induced to form nuclear condensates via liquid-liquid phase separation driven by intrinsically disordered regions. Importantly, the phase separation property is required for the function of SR30 in disease susceptibility and the regulation of genes AS. Knockout of SR30 via CRISPR/Cas9 improves tomato disease resistance to P. infestans, P. capsici, and P. parasitica by promoting defense genes AS. These findings uncover a novel mechanism in a phase-separated protein that regulates plant immunity by altering the AS of defense-related genes and provides a new paradigm for engineering protein condensate in crop-resistant breeding.

摘要

可变剪接(AS)在植物与微生物的相互作用中起着至关重要的作用。调控宿主前体mRNA的可变剪接是多种病原体用来破坏植物免疫的关键策略。然而,宿主剪接因子调节植物免疫的潜在机制仍知之甚少。在此,鉴定出一种植物保守的富含丝氨酸/精氨酸(SR)的RNA剪接因子SR30,它对番茄抵御臭名昭著的致病疫霉(P. infestans)的免疫反应起负调控作用。SR30在全基因组水平上调控番茄mRNA的可变剪接,并抑制与防御相关基因的可变剪接。在致病疫霉感染期间,SR30通过由内在无序区域驱动的液-液相分离被诱导形成核凝聚物。重要的是,相分离特性是SR30在疾病易感性和基因可变剪接调控中发挥功能所必需的。通过CRISPR/Cas9敲除SR30可通过促进防御基因的可变剪接来提高番茄对致病疫霉、辣椒疫霉和寄生疫霉的抗病性。这些发现揭示了一种相分离蛋白通过改变与防御相关基因的可变剪接来调节植物免疫的新机制,并为作物抗病育种中工程化蛋白质凝聚物提供了新的范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/cdef49371c5a/ADVS-12-2500072-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/492ab5fa862f/ADVS-12-2500072-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/496f439ba0e3/ADVS-12-2500072-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/95999cd1c227/ADVS-12-2500072-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/2c546e999502/ADVS-12-2500072-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/a620c8a3475c/ADVS-12-2500072-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/cdef49371c5a/ADVS-12-2500072-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/492ab5fa862f/ADVS-12-2500072-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/496f439ba0e3/ADVS-12-2500072-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/95999cd1c227/ADVS-12-2500072-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/2c546e999502/ADVS-12-2500072-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/a620c8a3475c/ADVS-12-2500072-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c548/12279203/cdef49371c5a/ADVS-12-2500072-g002.jpg

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本文引用的文献

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Annu Rev Plant Biol. 2025 May;76(1):687-717. doi: 10.1146/annurev-arplant-083123-090055. Epub 2025 Feb 14.
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Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome.转录组范围的剪接网络揭示了核心剪接体的专门调控功能。
Science. 2024 Nov;386(6721):551-560. doi: 10.1126/science.adn8105. Epub 2024 Oct 31.
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Alternative splicing regulation in plants by SP7-like effectors from symbiotic arbuscular mycorrhizal fungi.
共生丛枝菌根真菌的 SP7 样效应物对植物可变剪接的调控。
Nat Commun. 2024 Aug 19;15(1):7107. doi: 10.1038/s41467-024-51512-5.
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The mA reader SlYTH2 negatively regulates tomato fruit aroma by impeding the translation process.mA 阅读器 SlYTH2 通过阻碍翻译过程来负调控番茄果实香气。
Proc Natl Acad Sci U S A. 2024 Jul 9;121(28):e2405100121. doi: 10.1073/pnas.2405100121. Epub 2024 Jul 1.
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Alternative splicing of a potato disease resistance gene maintains homeostasis between growth and immunity.马铃薯抗病基因的可变剪接维持生长和免疫之间的平衡。
Plant Cell. 2024 Sep 3;36(9):3729-3750. doi: 10.1093/plcell/koae189.
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SnapShot: Condensates in plant biology.快照:植物生物学中的凝聚物。
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Genome organization around nuclear speckles drives mRNA splicing efficiency.基因组在核斑周围的组织驱动 mRNA 剪接效率。
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