An LTR retrotransposon-derived lncRNA interacts with RNF169 to promote homologous recombination
An LTR retrotransposon-derived lncRNA interacts with RNF169 to promote homologous recombination
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LTR逆转录转座子衍生的lncRNA与RNF169相互作用促进同源重组
DOI：
10.15252/embr.201847650
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发表时间：
2019-09-05
期刊：
影响因子：
7.7
通讯作者：
Qu, Lianghu
中科院分区：
文献类型：
--
作者：
Deng, Bing;Xu, Wenli;Qu, Lianghu
LTR反转录转座子是人类基因组中丰富的重复元件，但其功能仍然知之甚少。在这里，我们报告的ERV-9 LTR反转录转座子衍生的lncRNA称为p53调节lncRNA同源重组（HR）修复1（PRLH 1）在人类细胞中的功能和调控机制。PRLH 1在p53突变的肝细胞癌（HCC）样品中高度表达，并促进p53突变的HCC细胞中的细胞增殖，并且其转录由NF-Y促进并由p53抑制。机制上，PRLH 1通过其5 '末端区域中的两个GCUUCA盒特异性结合到RNF 169的未表征结构域，以形成DNA修复复合物，其在双链断裂（DSB）位点取代53 BP 1，然后促进HR修复的起始。值得注意的是，PRLH 1对于RNF 169的稳定是必不可少的，作为RNA平台来募集和组装HR蛋白因子。这项研究的特点PRLH 1作为一种新的HR促进因子，并提供了新的见解LTR反转录转座子衍生的lncRNA的功能和机制。
LTR retrotransposons are abundant repetitive elements in the human genome, but their functions remain poorly understood. Here, we report the function and regulatory mechanism of an ERV-9 LTR retrotransposon-derived lncRNA called p53-regulated lncRNA for homologous recombination (HR) repair 1 (PRLH1) in human cells. PRLH1 is highly expressed in p53-mutated hepatocellular carcinoma (HCC) samples and promotes cell proliferation in p53-mutated HCC cells, and its transcription is promoted by NF-Y and suppressed by p53. Mechanistically, PRLH1 specifically binds to an uncharacterized domain of RNF169 through two GCUUCA boxes in its 5 ' terminal region to form a DNA repair complex that supplants 53BP1 at double-strand break (DSB) sites and then promotes the initiation of HR repair. Notably, PRLH1 is essential for the stabilization of RNF169, acting as an RNA platform to recruit and assemble HR protein factors. This study characterizes PRLH1 as a novel HR-promoting factor and provides new insights into the function and mechanism of LTR retrotransposon-derived lncRNAs.