miR-128 通过直接结合到 L1 RNA 来抑制 L1 反转录转座。
miR-128 represses L1 retrotransposition by binding directly to L1 RNA.
机构信息
Department of Molecular Biology and Biochemistry, Francisco J. Ayala School of Biological Sciences, University of California, Irvine, Irvine, California, USA.
Regulus Therapeutics, San Diego, California, USA.
出版信息
Nat Struct Mol Biol. 2015 Oct;22(10):824-31. doi: 10.1038/nsmb.3090. Epub 2015 Sep 14.
Long interspersed element 1 (LINE-1 or L1) retrotransposons compose 17% of the human genome. Active L1 elements are capable of replicative transposition (mobilization) and can act as drivers of genetic diversity. However, this mobilization is mutagenic and may be detrimental to the host, and therefore it is under strict control. Somatic cells usually silence L1 activity by DNA methylation of the L1 promoter. In hypomethylated cells, such as cancer cells and induced pluripotent stem cells (iPSCs), a window of opportunity for L1 reactivation emerges, and with it comes an increased risk of genomic instability and tumorigenesis. Here we show that miR-128 represses new retrotransposition events in human cancer cells and iPSCs by binding directly to L1 RNA. Thus, we have identified and characterized a new function of microRNAs: mediating genomic stability by suppressing the mobility of endogenous retrotransposons.
长散布元件 1（LINE-1 或 L1）逆转录转座子构成人类基因组的 17%。活跃的 L1 元件能够进行复制转位（移动），并可作为遗传多样性的驱动因素。然而，这种移动是诱变的，可能对宿主有害，因此受到严格控制。体细胞通常通过 L1 启动子的 DNA 甲基化使 L1 活性沉默。在低甲基化的细胞中，如癌细胞和诱导多能干细胞（iPSCs），L1 重新激活的机会之窗出现，随之而来的是基因组不稳定性和肿瘤发生的风险增加。在这里，我们通过直接结合 L1 RNA 显示 miR-128 抑制人类癌细胞和 iPSCs 中的新逆转录转座事件。因此，我们已经确定并描述了 microRNAs 的一个新功能：通过抑制内源性逆转录转座子的移动来介导基因组稳定性。
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