The transcription factor CfHac1 regulates the degradation of ubiquitin-mediated ER-associated misfolded proteins and pathogenicity in Colletotrichum fructicola

Abstract

During interactions, pathogenic fungi are subjected to endoplasmic reticulum (ER) stress from the host plants, resulting in the activation of the unfolded protein response (UPR) pathway. We identified the bZIP transcription factor CfHac1 in C. fructicola, which is a pathogenic organism implicated in a variety of plant diseases, and we found it to be crucial for the ER stress response and pathogenicity. However, the role of CfHac1 in regulating the degradation of ER-associated misfolded proteins remains unclear. In this study, we discovered that the CfHAC1 gene regulates conidial production, appressorium formation, response to ER stress, and pathogenicity through unconventional splicing. Further research revealed that the CfHAC1 gene also affects the ubiquitination of ER-associated misfolded proteins and mediates their degradation. We further identified two ubiquitin ligase genes, CfHRD1 and CfHRD3, that exhibit significant down-regulation in the ΔCfhac1 mutant strain. Subsequent investigations revealed that the CfHAC1 gene affects CfHRD1 and CfHRD3 expression through unconventional splicing, with both genes managing the degradation of ER-associated misfolded proteins via ubiquitination and influencing C. fructicola pathogenicity. Taken together, our results reveal a mechanism by which the transcription factor CfHac1 affects the expression of the ubiquitin ligase genes CfHRD1 and CfHRD3, leading to the ubiquitination and degradation of ER-associated misfolded proteins and pathogenicity. This provides a theoretical basis for the development of novel agents targeting key genes within this pathway.

Keywords

CfHAC1 gene / Unconventional splicing / Ubiquitination / ER-associated misfolded protein / Pathogenicity

References

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Funding

National Natural Science Foundation of China(32071765)

RIGHTS & PERMISSIONS

The Author(s)