PMID- 35693184 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1664-462X (Print) IS - 1664-462X (Electronic) IS - 1664-462X (Linking) VI - 13 DP - 2022 TI - Activation of NLR-Mediated Autoimmunity in Arabidopsis Early in Short Days 4 Mutant. PG - 881212 LID - 10.3389/fpls.2022.881212 [doi] LID - 881212 AB - From a reverse genetic screen using CRISPR/Cas9 gene editing tool, we unintentionally identified an autoimmune mutant. Map-based cloning and whole-genome sequencing revealed that it contains a deletion in SMALL UBIQUITIN-RELATED MODIFIER (SUMO) protease encoding gene EARLY IN SHORT DAYS 4 (ESD4). Previous studies reported that esd4 mutants accumulate elevated levels of plant defense hormone salicylic acid (SA). However, upregulated PATHOGENESIS-RELATED GENE 1 (PR1) expression in esd4 only partly relies on SA level. In this study, we show that plant metabolite N-hydroxypipecolic acid (NHP) biosynthetic genes are upregulated in esd4, and NHP biosynthesis mutant flavin-dependent-monooxygenase 1 (fmo1) partially suppresses the autoimmune phenotypes of esd4, suggestive of a requirement of NHP signaling for the autoimmunity in esd4. As activation of nucleotide-binding leucine-rich repeat immune receptors (NLRs) are associates with the biosynthesis of SA and NHP and lipase-like protein ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) is a key component downstream of many NLRs, we examined the relationship between EDS1 and ESD4 by analyzing the eds1 esd4 double mutant. We found that eds1 largely suppresses esd4 autoimmunity and blocks the elevated expressions of SA and NHP biosynthesis-related genes in esd4. Overall, our study provides evidence supporting the hypothesis that SUMO protease ESD4 likely targets a yet to be identified guardee of NLR by removing its SUMO modification to avoid recognition by the cognate NLR. Loss of ESD4 results in activation of NLR-mediated autoimmunity. CI - Copyright (c) 2022 Huang, Liu, Huang, Fernando, Li and Xia. FAU - Huang, Xingchuan AU - Huang X AD - Hunan Provincial Key Laboratory of Phytohormones and Growth Development, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China. AD - Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada. FAU - Liu, Yanan AU - Liu Y AD - Hunan Provincial Key Laboratory of Phytohormones and Growth Development, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China. FAU - Huang, Jianhua AU - Huang J AD - Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada. AD - Department of Botany, University of British Columbia, Vancouver, BC, Canada. FAU - Fernando, W G Dilantha AU - Fernando WGD AD - Department of Plant Science, University of Manitoba, Winnipeg, MB, Canada. FAU - Li, Xin AU - Li X AD - Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada. AD - Department of Botany, University of British Columbia, Vancouver, BC, Canada. FAU - Xia, Shitou AU - Xia S AD - Hunan Provincial Key Laboratory of Phytohormones and Growth Development, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China. LA - eng PT - Journal Article DEP - 20220525 PL - Switzerland TA - Front Plant Sci JT - Frontiers in plant science JID - 101568200 PMC - PMC9174647 OTO - NOTNLM OT - EDS1 OT - ESD4 OT - NHP signaling OT - NLR OT - SUMO modification OT - autoimmunity COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/06/14 06:00 MHDA- 2022/06/14 06:01 PMCR- 2022/01/01 CRDT- 2022/06/13 03:11 PHST- 2022/02/22 00:00 [received] PHST- 2022/05/04 00:00 [accepted] PHST- 2022/06/13 03:11 [entrez] PHST- 2022/06/14 06:00 [pubmed] PHST- 2022/06/14 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fpls.2022.881212 [doi] PST - epublish SO - Front Plant Sci. 2022 May 25;13:881212. doi: 10.3389/fpls.2022.881212. eCollection 2022.