U2AF - Hypoxia-induced fas alternative splicing regulator
Autor: | Ruta Zinkeviciute, Laurynas Vilys, Yuichi Makino, Egle Jakubauskiene, Arvydas Kanopka, Inga Peciuliene |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Gene isoform Biology medicine.disease_cause 03 medical and health sciences Exon 0302 clinical medicine RNA Precursors medicine Humans Protein Isoforms RNA Messenger fas Receptor Hypoxia Messenger RNA Alternative splicing Cell Biology Hypoxia (medical) HCT116 Cells Splicing Factor U2AF Cell biology Alternative Splicing Transmembrane domain 030104 developmental biology 030220 oncology & carcinogenesis RNA splicing medicine.symptom Carcinogenesis |
Zdroj: | Experimental Cell Research. 399:112444 |
ISSN: | 0014-4827 |
DOI: | 10.1016/j.yexcr.2020.112444 |
Popis: | 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 disease states. Recent studies have revealed that tumorigenesis and hypoxia are involved in large-scale alterations in alternative pre-mRNA splicing. Fas pre-mRNA is alternatively spliced by excluding exon 6 to produce soluble Fas (sFas) protein that lacks a transmembrane domain and acts by inhibiting Fas mediated apoptosis. In the present study we show that U2AF is involved in hypoxia dependent anti-apoptotic Fas mRNA isoform formation. Our performed studies show that U2AF-RNA interaction is reduced in hypoxic cells, leading to reduction of Fas and increased sFas mRNAs formation. Efficient U2AF-RNA interactions of both subunits are important for Fas exon 6 inclusion into forming mRNA in normoxic and hypoxic cells. |
Databáze: | OpenAIRE |
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