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Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes

机译：L1逆转录转座子对转录的破坏及其对哺乳动物转录组的影响

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摘要

LINE-1 (L1) elements are the most abundant autonomous retrotransposons in the human genome, accounting for about 17% of human DNA. The L1 retrotransposon encodes two proteins, open reading frame (ORF)1 and the ORF2 endonuclease/reverse transcriptase. L1 RNA and ORF2 protein are difficult to detect in mammalian cells, even in the context of overexpression systems. Here we show that inserting L1 sequences on a transcript significantly decreases RNA expression and therefore protein expression. This decreased RNA concentration does not result from major effects on the transcription initiation rate or RNA stability. Rather, the poor L1 expression is primarily due to inadequate transcriptional elongation. Because L1 is an abundant and broadly distributed mobile element, the inhibition of transcriptional elongation by L1 might profoundly affect expression of endogenous human genes. We propose a model in which L1 affects gene expression genome-wide by acting as a 'molecular rheostat' of target genes. Bioinformatic data are consistent with the hypothesis that L1 can serve as an evolutionary fine-tuner of the human transcriptome.
机译：LINE-1（L1）元素是人类基因组中最丰富的自主反转录转座子，约占人类DNA的17％。 L1反转录转座子编码两个蛋白，即开放阅读框（ORF）1和ORF2核酸内切酶/逆转录酶。即使在过度表达的系统中，也很难在哺乳动物细胞中检测到L1 RNA和ORF2蛋白。在这里，我们显示在转录本上插入L1序列会显着降低RNA表达，从而降低蛋白表达。这种降低的RNA浓度不是由对转录起始速率或RNA稳定性的主要影响引起的。而是，较差的L1表达主要是由于转录延伸不足所致。因为L1是一个丰富且分布广泛的移动元件，所以L1对转录伸长的抑制可能会深刻影响内源性人类基因的表达。我们提出了一个模型，其中L1通过充当靶基因的“分子变阻器”来影响全基因组的基因表达。生物信息学数据与L1可以作为人类转录组的进化微调的假设相一致。

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