To determine whether conserved sut genes may play a role in tau mediated neurodegeneration in mammals, we have explored the translational potential of sut-2. We first identified sut-2 as a suppressor of tau-induced neurodegenerative defects in C. elegans [16]. The sut-2 gene encodes a zinc finger protein with a single conserved homolog in diverse species ranging from yeast to humans. The mammalian SUT-2 protein (MSUT2) binds to RNA and localizes to nuclear speckles, membraneless organelles coordinating mRNA processing in the nucleus [17, 18]. Knockout of the MSUT2 gene in mice results in animals that develop appropriately and appear healthy, live a normal lifespan, and exhibit normal neurological function including learning and memory [19]. We have shown that MSUT2 KO in mice can suppress tauopathy phenotypes in a transgenic mouse model expressing human tau protein. PS19 tau transgenic mice exhibit early stages of tauopathy by 3 months of age that progress to neurofibrillary degeneration by 8 months. These mice exhibit pathological tau and cognitive dysfunction resembling the changes observed in human AD patients or those with other tauopathy disorders. When combined
