Alternative splicing and protein function.

Alternative splicing and protein function.
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替代剪接和蛋白质功能。

DOI:
10.1186/1471-2105-6-266
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发表时间:
2005-11-07
期刊:
影响因子:
3
通讯作者:
Mironov AA
Mironov AA
中科院分区:
生物学4区
文献类型:
--
作者:
Neverov AD;Artamonova II;Nurtdinov RN;Frishman D;Gelfand MS;Mironov AA

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选择性剪接是高等真核生物产生蛋白质多样性的主要机制。虽然至少有一半,甚至更多的哺乳动物基因是选择性剪接的,但在不同的功能类别中,选择性剪接的频率是否相同还不清楚。EST对基因的不均匀覆盖和EST数据中的大量人为因素掩盖了这个问题。我们已经开发出一种方法,产生可能的mRNA异构体的EDAS数据库中包含的人类基因,考虑到无义介导的衰减和翻译起始规则的影响,并抵消不均匀EST覆盖的影响的程序。然后,我们计算了不同功能类别基因的mRNA亚型数量。编码核糖体蛋白的基因和“小GTP酶介导的信号转导”类别中的基因倾向于具有比平均值更少的同种型,而“DNA复制和染色体周期”类别中的基因具有比平均值更多的同种型。编码参与蛋白质-蛋白质相互作用的蛋白质的基因倾向于比编码非相互作用蛋白质的基因更频繁地选择性剪接,尽管选择性剪接基因的同种型的数量没有显著差异。过滤功能异构体满足生物学约束和accountung不均匀EST覆盖率允许我们描述不同功能类别的基因的选择性剪接的差异。这些观察结果似乎与基于当前生物学知识的预期一致:核糖体和信号转导蛋白的同种型较少,相互作用和细胞周期蛋白的选择性剪接较多。
Alternative splicing is a major mechanism of generating protein diversity in higher eukaryotes. Although at least half, and probably more, of mammalian genes are alternatively spliced, it was not clear, whether the frequency of alternative splicing is the same in different functional categories. The problem is obscured by uneven coverage of genes by ESTs and a large number of artifacts in the EST data. We have developed a method that generates possible mRNA isoforms for human genes contained in the EDAS database, taking into account the effects of nonsense-mediated decay and translation initiation rules, and a procedure for offsetting the effects of uneven EST coverage. Then we computed the number of mRNA isoforms for genes from different functional categories. Genes encoding ribosomal proteins and genes in the category "Small GTPase-mediated signal transduction" tend to have fewer isoforms than the average, whereas the genes in the category "DNA replication and chromosome cycle" have more isoforms than the average. Genes encoding proteins involved in protein-protein interactions tend to be alternatively spliced more often than genes encoding non-interacting proteins, although there is no significant difference in the number of isoforms of alternatively spliced genes. Filtering for functional isoforms satisfying biological constraints and accountung for uneven EST coverage allowed us to describe differences in alternative splicing of genes from different functional categories. The observations seem to be consistent with expectations based on current biological knowledge: less isoforms for ribosomal and signal transduction proteins, and more alternative splicing of interacting and cell cycle proteins.
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