An RNA splicing enhancer that does not act by looping.
An RNA splicing enhancer that does not act by looping.
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一种不通过环化起作用的 RNA 剪接增强子。
DOI：
10.1002/anie.201202932
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Lewis H
中科院分区：
文献类型：
--
作者：
Lewis H
哺乳动物前体mRNA剪接表现出丰富的替代位点和允许的组合。这将大多数基因的编码可能性扩大了几倍。剪接位点信号保守性差，通常很弱，但它们的使用通过与结合到内含子或外显子中的额外序列的蛋白质相互作用而增强。这些序列被称为剪接增强子，并且它们可以在距离靶剪接位点高达几百个核苷酸（nt）的距离处被发现。[1-4]大多数充分表征的外显子剪接增强子（ESEs）被SR蛋白结合。这些含有RNA结合结构域和富含丝氨酸-丝氨酸二肽的C-末端结构域（RS结构域）。它们稳定识别三种典型剪接信号的组分的结合：U1 snRNP，[5-7]其碱基配对到5о剪接位点，U2 AF蛋白，[8-10]其结合到3о剪接位点，和U2 snRNP，[11，12]其碱基配对到分支点。公认的ESE作用模型是RS结构域通过3D扩散在5о或3о剪接位点与靶蛋白或RNA双链体相遇，并在间插RNA中形成蛋白质桥接环（图1a）。然而，尽管这个模型已经有20年的历史了，但还没有能够对其进行明确的测试。有两条证据支持这一结论：1）RS结构域与ESE连接的模型底物的剪接速率（r）似乎与剪接位点和ESE之间的nt（n）数有关，正如对通过三维扩散相互作用的位点所预测的那样（r/n = 3/2）;[3] 2）通过UV光可以将NSE系留的RS结构域交联到剪接位点附近的RNA上，这表明它们非常接近。[13]这两个结果都不是决定性的。我们对速率数据的分析[3]表明，r/n_0 = 5/2或r/e_0 = kn，其中k是任意常数，这两个都不支持游离RNA的扩散模型。此外，如果整个SR蛋白可以结合ESE，那么
Mammalian pre-mRNA splicing exhibits an abundance of alternative sites and permissible combinations. This expands the coding possibilities of most genes by several-fold. The splice site signals are poorly conserved and often weak, but their use is augmented by interactions with proteins bound to additional sequences in the introns or exons. These sequences are known as splicing enhancers, and they can be found at distances up to several hundred nucleotides (nt) from the target splice sites.[1–4]Most well-characterized exonic splicing enhancers (ESEs) are bound by SRproteins. These contain RNA-binding domains and a C-terminal domain rich in arginine-serine dipeptides (RS domain). They stabilize the binding of components that recognize the three canonical splicing signals: U1 snRNPs,[5–7] which base-pair to 5о splice sites, U2AF protein,[8–10] which binds to 3о splice sites, and U2 snRNPs,[11, 12] which base-pair to branch points. The accepted model for the action of ESEs is that the RS domain encounters the target protein or RNA duplex at a 5о or 3о splice site by 3D diffusion and forms a protein-bridged loop in the intervening RNA (Figure 1 a). However, although this model is around 20 years old, it has not been possible to test it definitively. It is supported by two lines of evidence: 1) the rate of splicing (r) of a model substrate with an RS domain tethered to an ESE appeared to be related to the number of nt (n) between the splice site and the ESE, as predicted for sites interacting by 3D diffusion (r/nÀ3/2);[3] 2) an ESE-tethered RSdomain could be cross-linked by UV light to RNA near a splice site, demonstrating close proximity.[13] Neither of these results is conclusive. Our analysis of the rate data [3] suggests that r/nÀ5/2 or r/eÀkn, where k is an arbitrary constant, neither of which supports the diffusion model for free RNA. Moreover, if entire SR proteins can bind the ESE then the effects of the
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影响因子：
15
作者：
Presolski SI;Hong V;Cho SH;Finn MG
通讯作者：
Finn MG
人纤维蛋白原 Bβ 链基因外显子 7 中隐秘剪接位点的使用受到该外显子内天然沉默的 SF2/ASF 结合位点的调节。
影响因子：
4.5
作者：
S. Spena;M. Tenchini;E. Buratti
通讯作者：
E. Buratti
影响因子：
10.5
作者：
Shen, Haihong;Green, Michael R.
通讯作者：
Green, Michael R.
DOI：
10.1073/pnas.0500543102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Ibrahim, EC;Schaal, TD;Maniatis, T
通讯作者：
Maniatis, T
影响因子：
10.5
作者：
TIAN, M;MANIATIS, T
通讯作者：
MANIATIS, T