Unconventional translation of mammalian LINE-1 retrotransposons

Unconventional translation of mammalian LINE-1 retrotransposons
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DOI:
10.1101/gad.1380406
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发表时间:
2006-01-15
影响因子:
10.5
通讯作者:
Moran, JV
Moran, JV
中科院分区:
生物学1区
文献类型:
--
作者:
Alisch, RS;Garcia-Perez, JL;Moran, JV

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长散布的Element-1(LINE-1或L1)反转录转座子编码移动所需的蛋白质(ORF1p和ORF2p),但对L1mRNA是如何翻译的知之甚少。在这里,我们证明了ORF2的翻译一般始于ORF2的第一个框内蛋氨酸密码子,并且ORF1和ORF间隔区对于ORF2的翻译都是必不可少的。值得注意的是,将ORF2 Aug密码子改变为任何其他编码三联体都与逆转座兼容。然而,在ORF1中引入提前终止密码子或在ORF间隔区中引入耐热发夹,可将ORF2p翻译或L1逆转录转座减少到接近野生型水平的5%。从“天然”和密码子优化的“合成”小鼠L1获得的相似数据导致我们提出ORF2是通过非传统的终止/重新启动机制翻译的。
Long Interspersed Element-1 (LINE-1 or L1) retrotransposons encode proteins required for their mobility (ORF1p and ORF2p), yet little is known about how L1 mRNA is translated. Here, we show that ORF2 translation generally initiates from the first in-frame methionine codon of ORF2, and that both ORF1 and the inter-ORF spacer are dispensable for ORF2 translation. Remarkably, changing the ORF2 AUG codon to any other coding triplet is compatible with retrotransposition. However, introducing a premature termination codon in ORF1 or a thermostable hairpin in the inter-ORF spacer reduces ORF2p translation or L1 retrotransposition to similar to 5% of wild-type levels. Similar data obtained from "natural" and codon optimized "synthetic" mouse L1s lead us to propose that ORF2 is translated by an unconventional termination/ reinitiation mechanism.