In our previous genetic studies of tauopathy in C. elegans, we identified multiple genes whose loss of function suppress tauopathy neurodegenerative phenotypes (suppressor of tauopathy or sut genes). The largest group of sut genes isolated encode proteins residing in nuclear speckles, which suggests modulating nuclear speckle function can ameliorate tauopathy. Conserved sut genes may also play a role in tau mediated neurodegeneration in mammals. The first tauopathy suppressor isolated, sut-1, exhibits strong suppression of tauopathy phenotypes; SUT-1 protein localizes to nuclear speckles [13] and is thought to mediate spliceosome recycling [14]. The parn-2 gene is another recently isolated partial tau suppressor gene encoding a protein known to reside in nuclear speckles with poly(A) RNase activity [15].
