The role of hypoxia on Alzheimer's disease-related APP and Tau mRNA formation

The removal of introns from mRNA precursors (pre-mRNAs) is an essential step in eukaryotic gene expression. The splicing machinery heavily contributes to biological complexity and especially to the ability of cells to adapt to altered cellular conditions. Hypoxia also plays a key role in the pathophysiology of many diseases, including Alzheimer's disease (AD). In the presented study, we have examined the influence of cellular hypoxia on mRNA splice variant formation from Alzheimer's disease-related Tau and APP genes in brain cells. We have shown that the hypoxic microenvimnment influenced the formation of Tau mRNA splice variants, but had no effect on APP mRNA splice variant formation. Additionally, our presented results indicate that splicing factor SRSF1 but not SRSF5 alters the formation of Tau cellular mRNA splice variants in hypoxic cells. Obtained results have also shown that hypoxic brain cells possess enhanced CLKI-4 kinase mRNA levels. This study underlines that cellular hypoxia can influence disease development through changing pre-mRNA splicing.

Automated summary

This study investigated the influence of cellular hypoxia on mRNA splice variant formation from Alzheimer's disease-related Tau and APP genes, revealing that the hypoxic microenvironment affects Tau mRNA splice variant formation but not APP mRNA splice variant formation, and highlighting the role of splicing factor SRSF1 in this process.