Two isoforms of the T-cell intracellular antigen 1 (TIA-1) splicing factor display distinct splicing regulation activities -: Control of TIA-1 isoform ratio by TIA-1-related protein
Two isoforms of the T-cell intracellular antigen 1 (TIA-1) splicing factor display distinct splicing regulation activities -: Control of TIA-1 isoform ratio by TIA-1-related protein
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DOI：
10.1074/jbc.m700688200
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发表时间：
2007-07-06
影响因子：
4.8
通讯作者：
Valcarcel, Juan
中科院分区：
文献类型：
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作者：
Izquierdo, Jose M.;Valcarcel, Juan
TIA-1（T细胞胞内抗原1）和TIAR（TIA-1相关蛋白）是RNA结合蛋白，参与调节可变前mRNA剪接和RNA代谢的其他方面。这些蛋白质的各种异构体存在于哺乳动物中。例如，TIA- 1呈现由外显子5的选择性剪接产生的两种主要同种型（TIA-1a和TIA-1b），其除了TIA-1a同种型之外相差11个氨基酸。在这里，我们表明TIA-1和TIAR亚型的相对表达在不同的人体组织和细胞系中不同，表明不同的功能特性和受调节的亚型表达。我们报告，而TIA-1亚型显示出类似的亚细胞分布和RNA结合，TIA-1b显示增强的剪接刺激活性相比，TIA-1a，在体外和体内。有趣的是，从HeLa和小鼠胚胎成纤维细胞中去除TIAR导致TIA-1b/a表达比率增加，表明TIAR调节TIA-1亚型的相对表达。两者合计，结果揭示了TIA-1亚型的不同功能特性和控制亚型表达的调控网络的存在。
TIA-1 (T-cell Intracellular Antigen 1) and TIAR (TIA-1-related protein) are RNA-binding proteins involved in the regulation of alternative pre-mRNA splicing and other aspects of RNA metabolism. Various isoforms of these proteins exist in mammals. For example, TIA- 1 presents two major isoforms (TIA-1a and TIA-1b) generated by alternative splicing of exon 5 that differ by eleven amino acids exclusive of the TIA-1a isoform. Here we show that the relative expression of TIA-1 and TIAR isoforms varies in different human tissues and cell lines, suggesting distinct functional properties and regulated isoform expression. We report that whereas TIA-1 isoforms show similar subcellular distribution and RNA binding, TIA-1b displays enhanced splicing stimulatory activity compared with TIA-1a, both in vitro and in vivo. Interestingly, TIAR depletion from HeLa and mouse embryonic fibroblasts results in an increased ratio of TIA-1b/a expression, suggesting that TIAR regulates the relative expression of TIA-1 isoforms. Taken together, the results reveal distinct functional properties of TIA-1 isoforms and the existence of a regulatory network that controls isoform expression.