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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Laurynas Vilys, Inga Peciuliene, Egle Jakubauskiene, Ruta Zinkeviciute, Yuichi Makino, Arvydas Kanopka. U2AF - Hypoxia-induced fas alternative splicing regulator. Experimental cell research. 2021 Feb 01;399(1):112444

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PMID: 33347855

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