Increased noncanonical splicing of autoantigen transcripts provides the structural basis for expression of untolerized epitopes
Increased noncanonical splicing of autoantigen transcripts provides the structural basis for expression of untolerized epitopes
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DOI：
10.1016/j.jaci.2004.09.006
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发表时间：
2004-12-01
影响因子：
14.2
通讯作者：
Yang, XF
中科院分区：
文献类型：
--
作者：
Ng, B;Yang, F;Yang, XF
背景：选择性剪接对于从有限的基因组中增加人类蛋白质组的复杂性是重要的。以往的研究表明，对于一些自身抗原，有差异的免疫原性之间的选择性剪接isoform.Objectives：在这里，我们测试的假设，选择性剪接是一个共同的特点，自体蛋白的转录本是自身抗原。测试的推论假设是，nonautoantigen转录有一个较低的频率选择性splicing.Methods：选择性剪接的程度内45随机选择的自身免疫性疾病相关的蛋白质进行了比较，9554随机选择的蛋白质在人类基因组中，通过使用生物信息学分析。异构体特异性区域，导致选择性剪接的研究，其潜在的抗原表位抗体或T细胞receptor.Results：选择性剪接发生在100%的自身抗原转录本。这明显高于在9554个随机选择的人类基因转录本中观察到的大约42%的选择性剪接率（P
Background: Alternative splicing is important for increasing the complexity of the human proteome from a limited genome. Previous studies have shown that for some autoantigens, there is differential immunogenicity among alternatively spliced isoforms.Objectives: Herein, we tested the hypothesis that alternative splicing is a common feature for transcripts of autologous proteins that are autoantigens. The corollary hypothesis tested was that nonautoantigen transcripts have a lower frequency of alternative splicing.Methods: The extent of alternative splicing within 45 randomly selected self-proteins associated with autoimmune diseases was compared with 9554 randomly selected proteins in the human genome by using bioinformatics analyses. Isoform-specific regions that resulted from alternative splicing were studied for their potential to be epitopes for antibodies or T-cell receptors.Results: Alternative splicing occurred in 100% of the autoantigen transcripts. This was significantly higher than the approximately 42% rate of alternative splicing observed in the 9554 randomly selected human gene transcripts (P