A group of scientists from the Department of Immunology and Cell Biology, Institute of Biotechnology (BTI), Vilnius University Life Sciences Centre (VU GMC), led by Dr Arvydas Kanopka, has implemented the project Hypoxia as a cellular stress inducing mRNA diversity and ageing' (Nr. S-SEN-20-17) under the National Science Programme 'Healthy Ageing' of the Lithuanian Council of Science, and has made a recommendation based on the main results obtained during the implementation of this project.

Cells are stressed in response to changes in their microenvironment. Cell stress is caused by temperature fluctuations, changes in the pH of the microenvironment, increased or decreased oxygen concentration in the environment, nutrient deficiencies etc. Short-term environmental oxygen deprivation (hypoxia) primarily triggers a series of adaptive responses in cells to ensure that oxygen supply meets metabolic, bioenergetic and other needs. In the case of prolonged hypoxia, pre-mRNA splicing is altered, leading to the generation of different isoforms of mRNA. Proteins synthesised from these mRNA isoforms promote cell survival under reduced oxygen conditions.

The project 'Hypoxia as a cellular stress inducing mRNA diversity and ageing' set out to investigate the effects of brief hypoxia-induced cellular stress on the formation of mRNA isoforms in stress-responsive genes and to identify the splicing factors regulating hypoxia dependent alternative splicing.

The data obtained during the project showed that hypoxia alters gene expression and protein modification levels in cells, and thus the generation of mRNA isoforms from which proteins are synthesised to help cells adapt and survive in a hostile microenvironment. It was also found that one of the regulatory factors of hypoxic environment-dependent mRNA isoform formation is the heterodimeric splicing factor U2AF, which may be a potential target for the therapy of hypoxia-related diseases.

In summary, the results show that when cells are initially exposed to hypoxic conditions, they activate a response mechanism similar to that activated during cellular stress. Only later is the mechanism of adaptation to hypoxic conditions activated in cells.
The studies carried out extend the existing knowledge on the impact of reduced oxygen levels in the environment on cellular processes and have practical applications in the diagnosis and treatment of hypoxia-related diseases. Based on the results of the project, the team of researchers from the Immunology and Cell Biology Unit proposes to take into account the differences in cellular processes induced by short-term and long-term hypoxic conditions.

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