Exon-trapping mediated by the human retrotransposon SVA
Exon-trapping mediated by the human retrotransposon SVA
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DOI：
10.1101/gr.093153.109
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发表时间：
2009-11-01
期刊：
影响因子：
7
通讯作者：
Kazazian, Haig H., Jr.
中科院分区：
文献类型：
--
作者：
Hancks, Dustin C.;Ewing, Adam D.;Kazazian, Haig H., Jr.
虽然大多数人类逆转录转座子是无活性的，但无活性和活性逆转录转座子都驱动基因组进化，并可能通过各种机制影响转录。在人类中，三个逆转录转座子家族仍然活跃，但其中之一SVA仍然神秘。在这里，我们报告了一个新的SVA亚家族的鉴定，这显然是形成后的选择性剪接事件的MAST 2基因的第一个外显子剪接成内含子SVA，随后反转录。在其他灵长类动物基因组中也发现了由于剪接成SVA而使上游外显子反转录转座的其他例子。经过分子和计算实验，我们发现了许多功能39剪接位点在许多不同的转录SVAs在人类和黑猩猩的基因组。使用含有SVA的小基因剪接构建体，我们观察到细胞培养物中的剪接，沿着引入提前终止密码子（PTC）的SVA外显子化事件。这些数据意味着，一个SVA驻留在内含子中的基因相同的方向可能会改变正常的基因转录，无论是通过基因捕获或通过引入PTC通过外显子，可能会造成物种内和跨物种的差异。
Although most human retrotransposons are inactive, both inactive and active retrotransposons drive genome evolution and may influence transcription through various mechanisms. In humans, three retrotransposon families are still active, but one of these, SVA, remains mysterious. Here we report the identification of a new subfamily of SVA, which apparently formed after an alternative splicing event where the first exon of the MAST2 gene spliced into an intronic SVA and subsequently retrotransposed. Additional examples of SVA retrotransposing upstream exons due to splicing into SVA were also identified in other primate genomes. After molecular and computational experiments, we found a number of functional 39 splice sites within many different transcribed SVAs across the human and chimpanzee genomes. Using a minigene splicing construct containing an SVA, we observed splicing in cell culture, along with SVA exonization events that introduced premature termination codons (PTCs). These data imply that an SVA residing within an intron in the same orientation as the gene may alter normal gene transcription either by gene-trapping or by introducing PTCs through exonization, possibly creating differences within and across species.