The emergence of alternative 3' and 5' splice site exons from constitutive exons.
The emergence of alternative 3' and 5' splice site exons from constitutive exons.
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DOI：
10.1371/journal.pcbi.0030095
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发表时间：
2007-05
影响因子：
4.3
通讯作者：
Ast, Gil
中科院分区：
文献类型：
--
作者：
Koren, Eli;Lev-Maor, Galit;Ast, Gil
选择性3′和5′剪接位点（ss）事件是所有选择性剪接事件的重要组成部分。还发现这些事件与几种异常剪接疾病有关。然而，只有少数的特征，区分这些事件的替代盒外显子是已知的。在这项研究中，我们比较了组成型外显子，替代盒外显子，以及替代3′ss和5′ss外显子的特征。结果表明，交替3′ss和5′ss外显子是介于组成型外显子和交替盒式外显子之间的一种中间状态，其中组成侧类似于组成型外显子，交替侧类似于交替盒式外显子。结果还表明，选择性3′ss和5′ss外显子表现出低水平的对称性（框架保留），类似于组成型外显子，而两个选择性剪接位点之间的序列显示出高水平的对称性，类似于选择性盒外显子。此外，侧翼内含子的保守性分析表明，外显子的选择性剪接位点是至少9个核苷酸分开显示出高的保守性水平，表明内含子参与其剪接的调节，而外显子的选择性剪接位点是少于9个核苷酸分开显示出低的保守性水平。这些外显子，跨越7个脊椎动物物种的进一步检查，提出了一个进化模型，其中的替代状态是一个祖先的组成型外显子的衍生物，其中外显子内的突变或沿着侧翼内含子导致创建一个新的剪接位点，与原来的竞争，导致选择性剪接位点。该模型在四个外显子上进行了实验验证，表明它们确实起源于在进化过程中获得新的竞争剪接位点的组成型外显子。选择性剪接是负责从单个基因产生多个mRNA产物的机制。它被认为是基因组复杂性成就的关键参与者。选择性3′和5′剪接事件是所有选择性剪接事件的重要组成部分，其中一部分外显子在mRNA中被选择性地包含或排除，但对其调控机制和导致其产生的进化背景知之甚少。我们发现，选择性3′和5′剪接位点外显子类似于组成型外显子。然而，它们的替代序列类似于替代盒外显子。跨越7个脊椎动物物种的比较基因组学提出了一种进化模型，其中替代状态是祖先组成型外显子的衍生物，其中外显子内或沿着侧翼内含子的突变导致与原始剪接位点竞争的新剪接位点的产生，从而导致选择性剪接位点。该模型得到了实验验证，表明在进化过程中，突变使组成型外显子发生了3′和5′选择性剪接。
Alternative 3′ and 5′ splice site (ss) events constitute a significant part of all alternative splicing events. These events were also found to be related to several aberrant splicing diseases. However, only few of the characteristics that distinguish these events from alternative cassette exons are known currently. In this study, we compared the characteristics of constitutive exons, alternative cassette exons, and alternative 3′ss and 5′ss exons. The results revealed that alternative 3′ss and 5′ss exons are an intermediate state between constitutive and alternative cassette exons, where the constitutive side resembles constitutive exons, and the alternative side resembles alternative cassette exons. The results also show that alternative 3′ss and 5′ss exons exhibit low levels of symmetry (frame-preserving), similar to constitutive exons, whereas the sequence between the two alternative splice sites shows high symmetry levels, similar to alternative cassette exons. In addition, flanking intronic conservation analysis revealed that exons whose alternative splice sites are at least nine nucleotides apart show a high conservation level, indicating intronic participation in the regulation of their splicing, whereas exons whose alternative splice sites are fewer than nine nucleotides apart show a low conservation level. Further examination of these exons, spanning seven vertebrate species, suggests an evolutionary model in which the alternative state is a derivative of an ancestral constitutive exon, where a mutation inside the exon or along the flanking intron resulted in the creation of a new splice site that competes with the original one, leading to alternative splice site selection. This model was validated experimentally on four exons, showing that they indeed originated from constitutive exons that acquired a new competing splice site during evolution. Alternative splicing is the mechanism that is responsible for the creation of multiple mRNA products from a single gene. It is considered a key player in genomic complexity achievement. Alternative 3′ and 5′ splicing events in which part of the exon is alternatively included or excluded in the mRNA constitute a significant part of all alternative splicing events, and yet little is known regarding their regulation mechanism and the evolutionary background that led to their creation. We show that alternative 3′ and 5′ splice site exons resemble constitutive exons. However, their alternative sequence resembles alternative cassette exons. Comparative genomics spanning seven vertebrate species suggests an evolutionary model in which the alternative state is a derivative of an ancestral constitutive exon, where a mutation inside the exon or along the flanking intron resulted in the creation of a new splice site that competes with the original one, leading to alternative splice site selection. This model was validated experimentally, showing that during evolution mutations shifted constitutive exons to undergo alternative 3′ and 5′ splicing.
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影响因子：
4.5
作者：
Chern, Tzu-Ming;van Nimwegen, Erik;Kai, Chikatoshi;Kawai, Jun;Carninci, Piero;Hayashizaki, Yoshihide;Zavolan, Mihaela
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通讯作者：
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作者：
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通讯作者：
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作者：
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通讯作者：
Blencowe, BJ
在不寻常的gyngyn供体上，系统发育广泛的替代剪接。
影响因子：
12.3
作者：
Hiller, Michael;Huse, Klaus;Szafranski, Karol;Rosenstiel, Philip;Schreiber, Stefan;Backofen, Rolf;Platzer, Matthias
通讯作者：
Platzer, Matthias