Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-12-26 , DOI: 10.1016/j.yexcr.2020.112444 Laurynas Vilys , Inga Peciuliene , Egle Jakubauskiene , Ruta Zinkeviciute , Yuichi Makino , Arvydas Kanopka
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.
中文翻译:
U2AF-低氧诱导的fas替代剪接调节剂
剪接机制极大地促进了生物学的复杂性,尤其是细胞适应改变的细胞条件的能力。缺氧在许多疾病状态的病理生理中也起着关键作用。最近的研究表明,肿瘤发生和低氧参与了替代性的前mRNA剪接的大规模改变。通过排除第6外显子来剪接Fas pre-mRNA,以产生可溶的Fas(sFas)蛋白,该蛋白缺少跨膜结构域并通过抑制Fas介导的凋亡而发挥作用。
在本研究中,我们表明U2AF参与缺氧依赖性抗凋亡Fas mRNA同工型形成。我们进行的研究表明,低氧细胞中U2AF-RNA相互作用减少,导致Fas减少和sFas mRNA形成增加。两个亚基的有效U2AF-RNA相互作用对于Fas外显子6包涵在常氧和低氧细胞中形成mRNA至关重要。