SUMOylation regulates pre-mRNA splicing to overcome DNA damage in fungi

Pathogenic fungi are subject to DNA damage stress derived from host immune responses during infection. Small ubiquitin-like modifier (SUMO) modification and precursor (pre)-mRNA splicing are both involved in DNA damage response (DDR). However, the mechanisms of how SUMOylation and splicing coordinated in DDR remain largely unknown. Combining with biochemical analysis, RNA-Seq method, and biological analysis, we report that SUMO pathway participates in DDR and virulence in Fusarium graminearum, a causal agent of Fusarium head blight of cereal crops world-wide. Interestingly, a key transcription factor FgSR is SUMOylated upon DNA damage stress. SUMOylation regulates FgSR nuclear-cytoplasmic partitioning and its phosphorylation by FgMec1, and promotes its interaction with chromatin remodeling complex SWI/SNF for activating the expression of DDR-related genes. Moreover, the SWI/SNF complex was found to further recruit splicing-related NineTeen Complex, subsequently modulates pre-mRNA splicing during DDR. Our findings reveal a novel function of SUMOylation in DDR by regulating a transcription factor to orchestrate gene expression and pre-mRNA splicing to overcome DNA damage during the infection of F. graminearum, which advances the understanding of the delicate regulation of DDR by SUMOylation in pathogenic fungi, and extends the knowledge of cooperation of SUMOylation and pre-mRNA splicing in DDR in eukaryotes.

Automated summary

This study reveals a novel function of SUMOylation in DNA damage response (DDR) and virulence in Fusarium graminearum, a causal agent of Fusarium head blight of cereal crops. It demonstrates that the transcription factor FgSR is SUMOylated upon DNA damage stress, which regulates its nuclear-cytoplasmic partitioning, phosphorylation, and interaction with chromatin remodeling complex SWI/SNF to activate the expression of DDR-related genes. Moreover, the SWI/SNF complex recruits splicing-related NineTeen Complex to modulate pre-mRNA splicing during DDR. These findings advance the understanding of the delicate regulation of DDR by SUMOylation in pathogenic fungi, and extend the knowledge of cooperation of SUMOylation and pre-mRNA splicing in DDR in eukaryotes.