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Multiple Fates of L1 Retrotransposition Intermediates in Cultured Human Cells

机译：L1逆转座中间体在培养的人类细胞中的多重命运

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LINE-1 (L1) retrotransposons comprise ～17% of human DNA, yet little is known about L1 integration. Here, we characterized 100 retrotransposition events in HeLa cells and show that distinct DNA repair pathways can resolve L1 cDNA retrotransposition intermediates. L1 cDNA resolution can lead to various forms of genetic instability including the generation of chimeric L1s, intrachromosomal deletions, intrachromosomal duplications, and intra-L1 rearrangements as well as a possible interchromosomal translocation. The L1 retrotransposition machinery also can mobilize U6 snRNA to new genomic locations, increasing the repertoire of noncoding RNAs that are mobilized by L1s. Finally, we have determined that the L1 reverse transcriptase can faithfully replicate its own transcript and has a base misincorporation error rate of ～1/7,000 bases. These data indicate that L1 retrotransposition in transformed human cells can lead to a variety of genomic rearrangements and suggest that host processes act to restrict L1 integration in cultured human cells. Indeed, the initial steps in L1 retrotransposition may define a host/parasite battleground that serves to limit the number of active L1s in the genome.
机译：LINE-1（L1）逆转座子约占人类DNA的17％，但对L1整合的了解却很少。在这里，我们表征了HeLa细胞中的100个逆转座事件，并表明不同的DNA修复途径可以解析L1 cDNA逆转座中间体。 L1 cDNA解析可能导致各种形式的遗传不稳定，包括嵌合L1的产生，染色体内缺失，染色体内重复和L1内重排以及可能的染色体间易位。 L1逆转录转座机制还可以将U6 snRNA动员到新的基因组位置，从而增加被L1动员的非编码RNA的库。最后，我们确定L1逆转录酶可以忠实地复制其自身的转录本，碱基错误掺入错误率约为1 / 7,000个碱基。这些数据表明，转化的人类细胞中的L1逆转座可以导致多种基因组重排，并表明宿主过程起着限制L1在培养的人类细胞中整合的作用。实际上，L1逆转座子的初始步骤可能会定义一个宿主/寄生虫战场，用于限制基因组中活跃L1的数量。

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