Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia.
Gene. 2013 Apr 15;518(2):231-41. doi: 10.1016/j.gene.2013.01.008. Epub 2013 Jan 17.
Retroelements are an abundant class of noncoding DNAs present in about half of the human genome. Among them, L1, Alu and SVA are currently active. They "jump" by retrotransposition, shuffle genomic regions by 5' and 3' transduction, and promote or inhibit gene transcription by providing alternative promoters or generating antisense and/or regulatory noncoding RNAs. Recent data also suggest that retroelement insertions into exons and introns of genes induce different types of genetic disease, including cancer. Retroelements interfere with the expression of genes by inducing alternative splicing via exon skipping and exonization using cryptic splice sites, and by providing polyadenylation signals. Here we summarize our current understanding of the molecular mechanisms of retroelement-induced mutagenesis which causes fifty different types of human disease. We categorize these mutagenic effects according to eleven different mechanisms and show that most of them may be explained either by traditional exon definition or transcriptional interference, a previously unrecognized molecular mechanism. In summary, this review gives an overview of retroelement insertions in genes that cause significant changes in their transcription and cotranscriptional splicing and show a remarkable level of complexity.
逆转录元件是一类丰富的非编码 DNA，存在于人类基因组的大约一半中。其中，L1、Alu 和 SVA 是目前活跃的。它们通过逆转录转座“跳跃”，通过 5' 和 3' 转导重排基因组区域，并通过提供替代启动子或产生反义及/或调控非编码 RNA 来促进或抑制基因转录。最近的数据还表明，逆转录元件插入基因的外显子和内含子会导致不同类型的遗传疾病，包括癌症。逆转录元件通过使用隐蔽剪接位点进行外显子跳跃和外显子化，以及提供聚腺苷酸化信号，干扰基因的表达，从而引起可变剪接。在这里，我们总结了我们对逆转录元件引起的诱变的分子机制的理解，这些诱变导致了五十种不同类型的人类疾病。我们根据十一种不同的机制对这些诱变效应进行分类，并表明其中大多数可以通过传统的外显子定义或转录干扰来解释，这是一种以前未被认识的分子机制。总之，这篇综述概述了导致基因转录和共转录剪接发生显著变化的基因中的逆转录元件插入，并显示出了显著的复杂性。
