DNA methylation-dependent epigenetic regulation of Verticillium dahliae virulence in plants.

As a conserved epigenetic mark, DNA cytosine methylation, at the 5' position (5-mC), plays important roles in multiple biological processes, including plant immunity. However, the involvement of DNA methylation in the determinants of virulence of phytopathogenic fungi remains elusive. In this study, we profiled the DNA methylation patterns of the phytopathogenic fungus Verticillium dahliae, one of the major causal pathogens of Verticillium wilt disease that causes great losses in many crops, and explored its contribution in fungal pathogenicity. We reveal that DNA methylation modification is present in V. dahliae and is required for its full virulence in host plants. The major enzymes responsible for the establishment of DNA methylation in V. dahliae were identified. We provided evidence that DNA methyltransferase-mediated establishment of DNA methylation pattern positively regulates fungal virulence, mainly through repressing a conserved protein kinase VdRim15-mediated Ca2+ signaling and ROS production, which is essential for the penetration activity of V. dahliae. In addition, we further demonstrated that histone H3 lysine 9 trimethylation (H3K9me3), another heterochromatin marker that is closely associated with 5-mC in eukaryotes, also participates in the regulation of V. dahliae pathogenicity, through a similar mechanism. More importantly, DNA methyltransferase genes VdRid, VdDnmt5, as well as H3K9me3 methyltransferase genes, were greatly induced during the early infection phase, implying that a dynamic regulation of 5-mC and H3K9me3 homeostasis is required for an efficient infection. Collectively, our findings uncover an epigenetic mechanism in the regulation of phytopathogenic fungal virulence. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00117-5.

A fungal effector suppresses the nuclear export of AGO1-miRNA complex to promote infection in plants.

Communication between interacting organisms via bioactive molecules is widespread in nature and plays key roles in diverse biological processes. Small RNAs (sRNAs) can travel between host plants and filamentous pathogens to trigger transkingdom RNA interference (RNAi) in recipient cells and modulate plant defense and pathogen virulence. However, how fungal pathogens counteract transkingdom antifungal RNAi has rarely been reported. Here we show that a secretory protein VdSSR1 (secretory silencing repressor 1) from Verticillium dahliae, a soil-borne phytopathogenic fungus that causes wilt diseases in a wide range of plant hosts, is required for fungal virulence in plants. VdSSR1 can translocate to plant nucleus and serve as a general suppressor of sRNA nucleocytoplasmic shuttling. We further reveal that VdSSR1 sequesters ALY family proteins, adaptors of the TREX complex, to interfere with nuclear export of the AGO1­microRNA (AGO1­miRNA) complex, leading to a great attenuation in cytoplasmic AGO1 protein and sRNA levels. With this mechanism, V. dahliae can suppress the accumulation of mobile plant miRNAs in fungal cells and succedent transkingdom silencing of virulence genes, thereby increasing its virulence in plants. Our findings reveal a mechanism by which phytopathogenic fungi antagonize antifungal RNAi-dependent plant immunity and expand the understanding on the complex interaction between host and filamentous pathogens.

A Combination of Human Embryonic Stem Cell-Derived Pancreatic Endoderm Transplant with LDHA-Repressing miRNA Can Attenuate High-Fat Diet Induced Type II Diabetes in Mice.

Type II diabetes mellitus (T2D) is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. The deficit and dysfunction of insulin secreting ß-cell are signature symptom for T2D. Additionally, in pancreatic ß-cell, a small group of genes which are abundantly expressed in most other tissues are highly selectively repressed. Lactate dehydrogenase A (LDHA) is one of such genes. Upregulation of LDHA is found in both human T2D and rodent T2D models. In this study, we identified a LDHA-suppressing microRNA (hsa-miR-590-3p) and used it together with human embryonic stem cell (hESC) derived pancreatic endoderm (PE) transplantation into a high-fat diet induced T2D mouse model. The procedure significantly improved glucose metabolism and other symptoms of T2D. Our findings support the potential T2D treatment using the combination of microRNA and hESC-differentiated PE cells.