Activation and repression functions of an SR splicing regulator depend on exonic versus intronic-binding position.
Activation and repression functions of an SR splicing regulator depend on exonic versus intronic-binding position.
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DOI：
10.1093/nar/gkr713
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发表时间：
2012-01
影响因子：
14.9
通讯作者：
Mattox W
中科院分区：
文献类型：
--
作者：
Shen M;Mattox W
SR蛋白及其相关因子在替代前mrna剪接中发挥广泛作用，并通过其富含arg - ser的效应域促进剪接位点识别。然而，SR调节因子与某些靶标的结合通过一种独特的机制导致剪接位点的抑制。在这里，我们研究了果蝇SR调节因子Transformer2的激活和抑制目标是如何引起其对剪接的不同影响的。我们发现，与激活一样，抑制也影响剪接位点识别和剪接体组装的早期步骤。调控元件的重新定位表明，通常从内含子位置抑制剪接的Tra2复合物在位于外显子时激活剪接。蛋白拴系实验表明，这种位置依赖性是Tra2的固有特性，并进一步表明抑制和激活是由该蛋白的单独效应域介导的。当从外显子位置激活剪接的其他果蝇SR因子（SF2和Rbp1）被内含地束缚时，它们既不能激活剪接，也不能抑制剪接。有趣的是，Tra2的两种活性都有利于围绕其结合位点的RNA序列的外显子身份。这提示了一个模型，其中这两个相反的功能协同作用，以确定交替剪接的外显子的位置和范围。
SR proteins and related factors play widespread roles in alternative pre-mRNA splicing and are known to promote splice site recognition through their Arg–Ser-rich effector domains. However, binding of SR regulators to some targets results in repression of splice sites through a distinct mechanism. Here, we investigate how activated and repressed targets of the Drosophila SR regulator Transformer2 elicit its differing effects on splicing. We find that, like activation, repression affects early steps in the recognition of splice sites and spliceosome assembly. Repositioning of regulatory elements reveals that Tra2 complexes that normally repress splicing from intronic positions activate splicing when located in an exon. Protein tethering experiments demonstrate that this position dependence is an intrinsic property of Tra2 and further show that repression and activation are mediated by separate effector domains of this protein. When other Drosophila SR factors (SF2 and Rbp1) that activate splicing from exonic positions were tethered intronically they failed to either activate or repress splicing. Interestingly, both activities of Tra2 favor the exonic identity of the RNA sequences that encompass its binding sites. This suggests a model in which these two opposite functions act in concert to define both the position and extent of alternatively spliced exons.
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DOI：
10.1073/pnas.1017700108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Cho, Suhyung;Hoang, Amy;Ghosh, Gourisankar
通讯作者：
Ghosh, Gourisankar
影响因子：
7
作者：
Ke, Shengdong;Shang, Shulian;Chasin, Lawrence A.
通讯作者：
Chasin, Lawrence A.
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Amir-Ahmady, B;Boutz, PL;Black, DL
通讯作者：
Black, DL
影响因子：
11.4
作者：
Kumar, S;Lopez, AJ
通讯作者：
Lopez, AJ