The role of hypoxia on Alzheimer’s disease-related APP and Tau mRNA formation
Autor: | Inga Pečiulienė, Eglė Jakubauskienė, Laurynas Vilys, Arvydas Kanopka |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Transcription Genetic tau Proteins Biology Amyloid beta-Protein Precursor 03 medical and health sciences Splicing factor 0302 clinical medicine Alzheimer Disease Cell Line Tumor Gene expression RNA Precursors Genetics medicine Humans RNA Messenger Gene Messenger RNA Alternative splicing Intron Brain General Medicine medicine.disease Cell Hypoxia Introns Cell biology Alternative Splicing 030104 developmental biology 030220 oncology & carcinogenesis RNA splicing Alzheimer's disease |
Zdroj: | Gene. 766:145146 |
ISSN: | 0378-1119 |
DOI: | 10.1016/j.gene.2020.145146 |
Popis: | 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 microenvironment 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 CLK1-4 kinase mRNA levels. This study underlines that cellular hypoxia can influence disease development through changing pre-mRNA splicing. |
Databáze: | OpenAIRE |
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