» Articles » PMID: 39880812

Genetically-encoded Targeted Protein Degradation Technology to Remove Endogenous Condensation-prone Proteins and Improve Crop Performance

Overview
Journal Nat Commun
Date 2025 Jan 29
PMID 39880812
Authors
Affiliations
Soon will be listed here.
Abstract

Effective modulation of gene expression in plants is achievable through tools like CRISPR and RNA interference, yet methods for directly modifying endogenous proteins remain lacking. Here, we identify the E3 ubiquitin ligase E3TCD1 and develope a Targeted Condensation-prone-protein Degradation (TCD) strategy. The X-E3TCD1 fusion protein acts as a genetically engineered degrader, selectively targeting endogenous proteins prone to condensation. For example, a transgenic E3TCD1 fusion with Teosinte branched 1 (TB1) degrades the native TB1 protein, resulting in increased tiller numbers in rice. Additionally, conditional degradation of the negative defense regulator Early Flowering 3 via a pathogen-responsive Pro-uORFs cassette enhances rice blast resistance without affecting flowering time in the absence of pathogen. Unlike prevailing targeted protein degradation strategies, the TCD system does not rely on small molecules, antibodies, or genetic knock-in fusion tags, demonstrating its promise as a transgene-based approach for optimizing crop performance.

References
1.
Wang W, Gu Y . The emerging role of biomolecular condensates in plant immunity. Plant Cell. 2021; 34(5):1568-1572. PMC: 9048959. DOI: 10.1093/plcell/koab240. View

2.
Ma Y, Miotk A, Sutikovic Z, Ermakova O, Wenzl C, Medzihradszky A . WUSCHEL acts as an auxin response rheostat to maintain apical stem cells in Arabidopsis. Nat Commun. 2019; 10(1):5093. PMC: 6841675. DOI: 10.1038/s41467-019-13074-9. View

3.
Zavaliev R, Mohan R, Chen T, Dong X . Formation of NPR1 Condensates Promotes Cell Survival during the Plant Immune Response. Cell. 2020; 182(5):1093-1108.e18. PMC: 7484032. DOI: 10.1016/j.cell.2020.07.016. View

4.
Klionsky D, Abdel-Aziz A, Abdelfatah S, Abdellatif M, Abdoli A, Abel S . Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021; 17(1):1-382. PMC: 7996087. DOI: 10.1080/15548627.2020.1797280. View

5.
Yi H, Shi H, Mao W, Yin J, Ma Y, Xu L . E3 ubiquitin ligase IPI1 controls rice immunity and flowering via both E3 ligase-dependent and -independent pathways. Dev Cell. 2024; 59(20):2719-2730.e4. DOI: 10.1016/j.devcel.2024.06.014. View