U2AF - Hypoxia-induced fas alternative splicing regulator

Autor: Ruta Zinkeviciute, Laurynas Vilys, Yuichi Makino, Egle Jakubauskiene, Arvydas Kanopka, Inga Peciuliene
Rok vydání: 2021
Předmět:
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