Ohms Stephen, Rangasamy Danny
John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
Oncotarget. 2014 Jun 30;5(12):4103-17. doi: 10.18632/oncotarget.1822.
Noncoding RNAs are key players in the maintenance of genomic integrity, particularly in silencing the expression of repetitive elements, some of which are retrotransposable and capable of causing genomic instability. Recent computational studies suggest an association between L1 expression and the generation of small RNAs. However, whether L1 expression has a role in the activation of small RNA expression has yet to be determined experimentally. Here we report a global analysis of small RNAs in deep sequencing from L1-active and L1-silenced breast cancer cells. We found that cells in which L1 expression was silenced exhibited greatly increased expression of a number of miRNAs and in particular, members of the let-7 family. In addition, we found differential expression of a few piRNAs that might potentially regulate gene expression. We also report the identification of several repeat RNAs against LTRs, LINEs and SINE elements. Although most of the repeat RNAs mapped to L1 elements, in general we found no significant differences in the expression levels of repeat RNAs in the presence or absence of L1 expression except for a few RNAs targeting subclasses of L1 elements. These differentially expressed small RNAs may function in human genome defence responses.
非编码RNA是维持基因组完整性的关键因素，尤其是在沉默重复元件的表达方面，其中一些重复元件是逆转座子，能够导致基因组不稳定。最近的计算研究表明L1表达与小RNA的产生之间存在关联。然而，L1表达是否在小RNA表达激活中起作用尚未通过实验确定。在这里，我们报告了对L1活跃和L1沉默的乳腺癌细胞深度测序中的小RNA进行的全局分析。我们发现，L1表达被沉默的细胞中，许多miRNA尤其是let-7家族成员的表达大幅增加。此外，我们发现了一些可能潜在调节基因表达的piRNA的差异表达。我们还报告了针对长末端重复序列（LTR）、长散在核元件（LINE）和短散在核元件（SINE）元件的几种重复RNA的鉴定。尽管大多数重复RNA映射到L1元件，但总体而言，除了少数靶向L1元件亚类的RNA外，我们发现无论有无L1表达，重复RNA的表达水平均无显著差异。这些差异表达的小RNA可能在人类基因组防御反应中发挥作用。
