SUMOylation regulates pre-mRNA splicing to overcome DNA damage in fungi
SUMOylation regulates pre-mRNA splicing to overcome DNA damage in fungi
复制标题
SUMOylation 调节 pre-mRNA 剪接以克服真菌中的 DNA 损伤
DOI：
10.1111/nph.18692
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发表时间：
2023-01-13
期刊：
影响因子：
9.4
通讯作者：
Yin，Yanni
中科院分区：
文献类型：
--
作者：
Jian，Yunqing;Chen，Xia;Yin，Yanni
病原真菌在感染过程中受到来自宿主免疫反应的DNA损伤应激。小泛素样修饰物（SUMO）修饰和前体（pre）-mRNA剪接都参与DNA损伤反应（DDR）。本研究结合生物化学分析、RNA-Seq方法和生物学分析，报道了SUMO通路参与了禾谷镰刀菌（Fusarium graminearum）的DDR和致病性。有趣的是，在DNA损伤应激时，一个关键的转录因子FgSR发生SUMO化，SUMO化调控FgSR的核质分配及其被FgMec 1磷酸化，并促进其与染色质重塑复合物SWI/SNF的相互作用，从而激活DDR相关基因的表达。此外，SWI/SNF复合物被发现进一步募集剪接相关的NineTeen Complex，随后调节DDR过程中的前mRNA剪接。我们的研究结果揭示了DDR中SUMO化的新功能，通过调节转录因子来协调基因表达和前mRNA剪接，以克服禾谷镰刀菌感染期间的DNA损伤，这推进了对SUMO化在病原真菌中对DDR的微妙调控的理解，并扩展了真核生物中DDR中SUMO化和前mRNA剪接的合作知识。
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 inFusarium 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 ofF. 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.