The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing
The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-mRNA splicing
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DOI：
10.1016/s1097-2765(00)00107-6
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发表时间：
2000-11-01
期刊：
影响因子：
16
通讯作者：
Valcárcel, J
中科院分区：
文献类型：
--
作者：
Förch, P;Puig, O;Valcárcel, J
我们在此报告，凋亡促进蛋白 TIA-1 调节果蝇基因雄性特异性致死 2 和人类凋亡基因 Fas 的选择性前 mRNA 剪接。 TIA-1 选择性地与包含 5' 剪接位点和富含 U 序列的前 mRNA 结合。 TIA-1 与富含 U 的片段结合有助于 U1 snRNP 识别 5' 剪接位点。该活性对于激活 msl-2 的弱 5' 剪接位点以及调节 Fas 中剪接位点配偶体的选择至关重要。与酿酒酵母剪接因子 Nam8 的结构和功能相似性表明，前 mRNA 剪接调节机制具有惊人的进化保守性，该机制控制着酵母减数分裂、果蝇剂量补偿或人类程序性细胞死亡等多种生物过程。
We report here that the apoptosis-promoting protein TIA-1 regulates alternative pre-mRNA splicing of the Drosophila melanogaster gene male-specific-lethal 2 and of the human apoptotic gene Fas. TIA-1 associates selectively with pre-mRNAs that contain 5' splice sites followed by U-rich sequences. TIA-1 binding to the U-rich stretches facilitates 5' splice site recognition by U1 snRNP. This activity is critical for activation of the weak 5' splice site of msl-2 and for modulating the choice of splice site partner in Fas. Structural and functional similarities with the Saccharomyces cerevisiae splicing factor Nam8 suggest striking evolutionary conservation of a mechanism of pre-mRNA splicing regulation that controls biological processes as diverse as meiosis in yeast, dosage compensation in fruit flies, or programmed cell death in humans.