Full-length human L1 insertions retain the capacity for high frequency retrotransposition in cultured cells
Full-length human L1 insertions retain the capacity for high frequency retrotransposition in cultured cells
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DOI：
10.1093/hmg/8.8.1557
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发表时间：
1999-08-01
影响因子：
3.5
通讯作者：
Kazazian, HH
中科院分区：
文献类型：
--
作者：
Kimberland, ML;Divoky, V;Kazazian, HH
功能性L1元件是能够插入人类基因并引起疾病的自主反转录转座子。迄今为止，12个已知的L1反转录转座到人类基因中的10个已被发现是5 '-截短的，并且不能进一步反转录转座。在这里，我们报告了两个全长L1元件的核苷酸序列，L1（β-thal）和L1（RP），它们分别插入到β-珠蛋白和视网膜色素变性2（RP 2）基因中。L1（β-thal）与活性人类L1的共有序列有99.4%相同，而L1（RP）有99.9%相同。这两个元件在培养的HeLa细胞中保留了令人印象深刻的高频率逆转录转座能力。事实上，L1（RP）是迄今为止分离的最活跃的L1。我们的数据表明，并非所有插入人类基因的L1都是“到达时死亡”的。我们的研究结果还进一步证实了顺式偏好的概念，即由特定L1编码的蛋白质优先作用于其编码RNA，而不是其他L1 RNA。
Functional L1 elements are autonomous retrotransposons that can insert into human genes and cause disease. To date, 10 of 12 known L1 retrotranspositions into human genes have been found to be 5'-truncated and incapable of further retrotransposition, Here we report the nucleotide sequences of the two full-length L1 elements, L1(beta-thal) and L1(RP), that have inserted into the beta-globin and retinitis pigmentosa-2 (RP2) genes, respectively. L1(beta-thal) is 99.4% identical to a consensus sequence of active human L1s, while L1(RP) is 99.9% identical. Both elements retain impressive capacity for high frequency retrotransposition in cultured HeLa cells, Indeed, L1(RP) is the most active L1 isolated to date, Our data indicate that not all L1 insertions into human genes are 'dead on arrival'. Our findings also lend further credence to the concept of cis preference, that the proteins encoded by a particular L1 preferentially act upon their encoding RNA as opposed to other L1 RNAs.