| Abstract [eng] |
Hypoxia is the term used to describe a reduction in the amount of oxygen in the cell's microenvironment, so that it is no longer sufficient to support normal cellular functions. Hypoxia is the most common pathological condition in ischaemic diseases and cancer and affects the progression of neurodegenerative diseases. One of the pathways in response to hypoxia is the altered expression of protein isoforms generated by alternative pre-mRNA splicing. Pre-mRNA splicing is one of the steps in mRNA maturation in which introns are removed from pre-mRNAs and exons are joined. Alternative splicing is a process where a single pre-mRNA can give rise to proteins with different or even opposing functions. Alternative splicing creates protein diversity, but changes in splicing can also lead to disease. In this work, we investigated the alternative splicing of the neurodegenerative disease-associated genes APP and TAU and its dependence on the hypoxic cell microenvironment. It is also shown that it is not only changes in the expression of splicing factors that regulate the hypoxia-dependent inclusion or omission of exon 6 of the FAS gene in the maturing mRNA. The level of modification of splicing factors also plays a crucial role in the regulation of alternative splicing. In this work, we discuss the discovery of a mechanism for hypoxia-dependent regulation of pre-mRNA splicing, which may be one of the key mechanisms regulating this process. |
