U1 small nuclear RNA (snRNA) is selectively enriched in 100% of familial Alzheimer's disease (AD) resulting from presenilin1 (PS1) and amyloid precursor protein (APP) mutations. However, it remains unknown what gene or protein cause the U1 snRNA overexpression and then resulted in AD. Using SH-SY5Y cells, we discovered that PS1 induced the overexpression of U1 snRNA, which increased the production of Aβ. Moreover, the U1 snRNA overexpression induced the upregulation of apoe and clu transcripts. In addition, the levels of phosphorylation of tau protein at Thr212 were significantly elevated in U1 snRNA overexpression cells. Immunofluorescence using antibodies reactive with the phosphorylation of tau at Thr212 site demonstrated the hyperphosphorylated tau localization with α-tubulin, the main component of cytoskeleton. Importantly, the increased levels of Bax, Bcl2, and Bax/Bcl2 ratio showed that the overexpression of U1 snRNA could cause cell apoptosis. Conclusively, these findings suggest that PS1 considerably increases the level of U1snRNA accompanied with the adverse change of Aβ level, AD-related tau cytoskeletal pathology, and cell apoptosis.
Keywords: Aβ; PS1; SH-SY5Y cells; Thr212; U1 snRNA.