Creation and disruption of protein features by alternative splicing -- a novel mechanism to modulate function.

Creation and disruption of protein features by alternative splicing -- a novel mechanism to modulate function.
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DOI:
10.1186/gb-2005-6-7-r58
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发表时间:
2005
期刊:
影响因子:
12.3
通讯作者:
Backofen R
Backofen R
中科院分区:
生物学1区
文献类型:
--
作者:
Hiller M;Huse K;Platzer M;Backofen R

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提出了一种新的选择性剪接机制,通过将两个不连续的外显子放在一起来创建蛋白质特征,并通过在其体内插入外显子来破坏蛋白质特征。对四种特定蛋白质特征的全基因组搜索提供了这种罕见机制的证据。选择性剪接通常发生在编码序列中并改变蛋白质结构和功能。它主要通过两种方式进行:跳过编码某种蛋白质特征的外显子,以及引入改变下游蛋白质序列的移码。这些机制广泛存在并得到充分研究。在这里,我们提出了一种额外的选择性剪接机制来调节蛋白质功能。这种机制通过将两个不连续的外显子放在一起来创建蛋白质特征,或者通过在其体内插入外显子来破坏蛋白质特征。与其他机制相比,该特征的各个部分都存在于两种拼接变体中,但该特征仅在两个部分合并的拼接形式中起作用。我们通过对四个蛋白质特征进行全基因组搜索,为该机制提供了证据:跨膜螺旋、磷酸化和糖基化位点以及 Pfam 结构域。我们描述了一种通过选择性剪接创建或删除蛋白质特征的新型事件。目前的数据表明这些事件很少见。除了这里研究的四个特征之外,这种机制对于许多其他蛋白质特征也是可以想象的,特别是对于小的线性蛋白质基序。它对于表征两种剪接形式的功能差异非常重要,并且应该在全基因组注释工作中予以考虑。此外,它还提供了一种从头开始预测选择性剪接事件的新策略。
A new mechanism of alternative splicing is proposed which creates a protein feature by putting together two non-consecutive exons and destroys a feature by inserting an exon in its body. Evidence for this rare mechanism is provided by a genome-wide search with four specific protein features. Alternative splicing often occurs in the coding sequence and alters protein structure and function. It is mainly carried out in two ways: by skipping exons that encode a certain protein feature and by introducing a frameshift that changes the downstream protein sequence. These mechanisms are widespread and well investigated. Here, we propose an additional mechanism of alternative splicing to modulate protein function. This mechanism creates a protein feature by putting together two non-consecutive exons or destroys a feature by inserting an exon in its body. In contrast to other mechanisms, the individual parts of the feature are present in both splice variants but the feature is only functional in the splice form where both parts are merged. We provide evidence for this mechanism by performing a genome-wide search with four protein features: transmembrane helices, phosphorylation and glycosylation sites, and Pfam domains. We describe a novel type of event that creates or removes a protein feature by alternative splicing. Current data suggest that these events are rare. Besides the four features investigated here, this mechanism is conceivable for many other protein features, especially for small linear protein motifs. It is important for the characterization of functional differences of two splice forms and should be considered in genome-wide annotation efforts. Furthermore, it offers a novel strategy for ab initio prediction of alternative splice events.
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发表时间: 2001-07-01
期刊: BIOINFORMATICS
影响因子: 5.8
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发表时间: 1999-12-17
影响因子: 5.6
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DOI: 10.1186/1471-2105-5-79
发表时间: 2004-06-22
期刊: BMC bioinformatics
影响因子: 3
作者:
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