Transcription-mediated gene fusion in the human genome
Transcription-mediated gene fusion in the human genome
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DOI：
10.1101/gr.4137606
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发表时间：
2006-01-01
期刊：
影响因子：
7
通讯作者：
Sorek, R
中科院分区：
文献类型：
--
作者：
Akiva, P;Toporik, A;Sorek, R
一个基因的转录通常在一个受调控的终止点结束，从而阻止RNA聚合酶“阅读下一个基因”。然而，零星的报告表明，在人类中存在嵌合转录体，即由两个连续的基因转录成一个RNA所形成的嵌合转录体。这种RNA的剪接和翻译导致了一种新的融合蛋白，具有来自两种原始蛋白的结构域。在这里，我们系统地鉴定了200多例人类基因组中的基因间剪接(涉及421个基因)，并实验证明至少有一半的融合存在于人类组织中。我们发现独特的剪接模式控制了转录本的功能和调节性质，并发现融合基因与非融合基因相比存在基因间距离偏差。我们证明，我们确定的数百个融合基因只是人类融合基因实际数量的一个子集。我们描述了一种新的进化机制，在这种机制中，转录诱导的嵌合体和逆转录导致了一个新的、活跃的融合基因。最后，我们提供了证据，证明转录诱导的嵌合体可能是促进蛋白质复合体进化的一种机制。
Transcription of a gene usually ends at a regulated termination point, preventing the RNA-polymerase from ' reading through the next gene. However, sporadic reports Suggest that chimeric transcripts, formed by transcription of two consecutive genes into one RNA, call Occur in human. The splicing and translation of such RNAs call lead to a new, fused protein, having domains from both original proteins. Here, we systematically identified over 200 cases of intergenic splicing in the human genome (involving 421 genes), and experimentally demonstrated that at least half of these fusions exist ill human tissues. We showed that unique splicing patterns dominate the functional and regulatory nature of the resulting transcripts, and found intergenic distance bias in fused compared with nonfused genes. We demonstrate that the hundreds Of fused genes we identified are only a Subset of the actual number of fused genes in human. We describe a novel evolutionary mechanism where transcription-induced chimerism followed by retroposition results in a new, active fused gene. Finally, we provide evidence that transcription-induced chimerism can be a mechanism contributing to the evolution of protein complexes.