How does Tra2β protein regulate tissue-specific RNA splicing?
How does Tra2β protein regulate tissue-specific RNA splicing?
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DOI：
10.1042/bst20120036
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发表时间：
2012-08
影响因子：
3.9
通讯作者：
Grellscheid S
中科院分区：
文献类型：
--
作者：
Elliott DJ;Best A;Dalgliesh C;Ehrmann I;Grellscheid S
剪接调节蛋白Tra2β在人类和昆虫之间是保守的，对小鼠发育至关重要。最近对生理RNA靶点的鉴定已经开始揭示Tra2β的分子靶点和作用机制。在转录组水平上，Tra2β蛋白结合了富含agaa序列的基质，这些序列通常指向外显子。特定的组织特异性选择性剪接外显子含有高浓度的高分Tra2β结合位点，并在体外强烈结合Tra2β。这些顶部外显子也通过共同表达Tra2β蛋白而被激活，并在Tra2β基因缺失后显著下调。Tra2β本身似乎在几种不同的小鼠组织中相当均匀地表达。在这里，我们回顾了Tra2β及其调控的靶外显子的特性，以及这种相当均匀表达的替代剪接调节剂可能驱动组织特异性剪接模式的机制。
The splicing regulator protein Tra2β is conserved between humans and insects and essential for mouse development. Recent identification of physiological RNA targets has started to uncover molecular targets and mechanisms of action of Tra2β. At a transcriptome-wide level, Tra2β protein binds a matrix of AGAA-rich sequences mapping frequently to exons. Particular tissue-specific alternatively spliced exons contain high concentrations of high scoring Tra2β binding sites and bind Tra2β strongly in vitro. These top exons were also activated for splicing inclusion in cellulo by co-expression of Tra2β protein and significantly down-regulated after genetic depletion of Tra2β. Tra2β itself seems to be fairly evenly expressed across several different mouse tissues. Here we review the properties of Tra2β and its regulated target exons, and mechanisms through which this fairly evenly expressed alternative splicing regulator might drive tissue-specific splicing patterns.