Computational analysis of splicing errors and mutations in human transcripts.
Computational analysis of splicing errors and mutations in human transcripts.
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人类笔录中剪接误差和突变的计算分析。
DOI：
10.1186/1471-2164-9-13
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发表时间：
2008-01-14
期刊：
影响因子：
4.4
通讯作者：
Gelfand, Mikhail S.
中科院分区：
文献类型：
--
作者：
Kurmangaliyev, Yerbol Z.;Gelfand, Mikhail S.
在高通量测序项目生成的人类cdna中发现的大多数保留内含子似乎是由欠剪接转录物引起的，因此它们捕获了前mrna剪接的中间步骤。另一方面，剪接位点的突变导致相应外显子的外显子跳变或先前存在的隐位点的激活。这两种类型的事件都反映了剪接机制的特性。保留的内含子明显短于组成的内含子，跳过的外显子明显短于具有隐位的外显子。保留内含子的供体和受体剪接位点均弱于组成内含子的剪接位点。受突变影响的真实受体位点在具有激活隐位的外显子中明显弱于在跳过的外显子中。与外显子跳变事件相比，在激活的隐式位点的情况下，从突变剪接位点到最近的等效位点的距离显着缩短。基因内保留内含子的发生率沿5′-3′方向单调增加（靠近3′端保留的内含子较多），与共转录剪接模型一致。保留内含子的外显子剪接增强子的密度比组成内含子高，外显子剪接沉默子的密度比跳过的外显子低。因此，对人类cDNA中保留的内含子、剪接位点突变导致的外显子跳过以及具有隐位点的外显子的分析结果与短内含子剪接、共转录剪接、剪接效率依赖于剪接位点强度以及候选外显子剪接增强子和沉默子密度的内含子定义机制一致。这些结果与最近发表的其他分析一致。
Most retained introns found in human cDNAs generated by high-throughput sequencing projects seem to result from underspliced transcripts, and thus they capture intermediate steps of pre-mRNA splicing. On the other hand, mutations in splice sites cause exon skipping of the respective exon or activation of pre-existing cryptic sites. Both types of events reflect properties of the splicing mechanism. The retained introns were significantly shorter than constitutive ones, and skipped exons are shorter than exons with cryptic sites. Both donor and acceptor splice sites of retained introns were weaker than splice sites of constitutive introns. The authentic acceptor sites affected by mutations were significantly weaker in exons with activated cryptic sites than in skipped exons. The distance from a mutated splice site to the nearest equivalent site is significantly shorter in cases of activated cryptic sites compared to exon skipping events. The prevalence of retained introns within genes monotonically increased in the 5'-to-3' direction (more retained introns close to the 3'-end), consistent with the model of co-transcriptional splicing. The density of exonic splicing enhancers was higher, and the density of exonic splicing silencers lower in retained introns compared to constitutive ones and in exons with cryptic sites compared to skipped exons. Thus the analysis of retained introns in human cDNA, exons skipped due to mutations in splice sites and exons with cryptic sites produced results consistent with the intron definition mechanism of splicing of short introns, co-transcriptional splicing, dependence of splicing efficiency on the splice site strength and the density of candidate exonic splicing enhancers and silencers. These results are consistent with other, recently published analyses.
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影响因子：
14.9
作者：
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通讯作者：
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