Niu Ruixia, Luo Ming, Wen Qing, Xiong Yifan, Dang Hua, Xu Guoyong
State Key Laboratory of Hybrid Rice, Hubei Provincial Research Center for Basic Biological Sciences, Institute for Advanced Studies (IAS), Wuhan University, Wuhan, Hubei 430072, China.
State Key Laboratory of Hybrid Rice, Hubei Provincial Research Center for Basic Biological Sciences, Institute for Advanced Studies (IAS), Wuhan University, Wuhan, Hubei 430072, China; Hubei Hongshan Laboratory, Wuhan, Hubei 430070, China; RNA Institute, Wuhan University, Wuhan, Hubei 430072, China.
Mol Plant. 2025 Jun 25. doi: 10.1016/j.molp.2025.06.013.
Gene expression can be modulated at the DNA, RNA, or protein level, with targeted protein degradation (TPD) representing a well-established and effective strategy for directly manipulating protein function. TPD enables selective elimination of proteins, protein condensates or organelles by co-opting cellular degradation pathways-such as the ubiquitin-proteasome system, autophagy, or endocytosis-via induced proximity mechanisms. While TPD has had transformative impacts in biomedical research over the past two decades, its application in plant science has lagged behind. This gap stems from the sequential dominance of RNA interference and CRISPR technologies, as well as the complexity and cost of implementing chemical, macromolecular, and recombinant degrader platforms in plants. The recent development of genetically encoded chimeric protein degraders (GE-CPDs) offers a timely and promising alternative. These transgene-based systems provide a plant-adaptable, precise, tunable, and conditional means to control endogenous protein levels, opening new avenues for studying dynamic biological processes and engineering complex traits in crops. As genome engineering technologies continue to advance, GE-CPDs are poised to become a versatile and scalable platform for both basic plant biology and agricultural innovation. In this review, we highlight five key opportunities-Selective-Targeting, Co-Targeting, Organelle-Targeting, Conditional-Targeting, and Synthetic-Engineering (SCOCS)-that illustrate the emerging importance of TPD technologies, particularly GE-CPDs, in advancing plant science. We argue that the field is now well-positioned to harness the full potential of TPD for next-generation crop improvement.
基因表达可以在DNA、RNA或蛋白质水平上进行调控，靶向蛋白质降解（TPD）是一种成熟且有效的直接操纵蛋白质功能的策略。TPD通过诱导邻近机制，利用细胞降解途径，如泛素-蛋白酶体系统、自噬或内吞作用，实现对蛋白质、蛋白质凝聚物或细胞器的选择性清除。虽然TPD在过去二十年的生物医学研究中产生了变革性影响，但其在植物科学中的应用却滞后了。这种差距源于RNA干扰和CRISPR技术的相继主导地位，以及在植物中实施化学、大分子和重组降解平台的复杂性和成本。基因编码嵌合蛋白降解剂（GE-CPDs）的最新发展提供了一个及时且有前景的替代方案。这些基于转基因的系统提供了一种适用于植物的、精确的、可调节的和有条件的手段来控制内源蛋白质水平，为研究动态生物学过程和改良作物复杂性状开辟了新途径。随着基因组工程技术的不断进步，GE-CPDs有望成为基础植物生物学和农业创新的通用且可扩展的平台。在本综述中，我们强调了五个关键机遇——选择性靶向、共靶向、细胞器靶向、条件靶向和合成工程（SCOCS），这些机遇说明了TPD技术，特别是GE-CPDs在推动植物科学发展中的重要性日益凸显。我们认为，该领域现在已具备充分利用TPD的全部潜力来实现下一代作物改良的条件。
