Medical Sciences Program, Indiana University, Bloomington, IN 47405, USA.
Nucleic Acids Res. 2012 Sep 1;40(17):8637-45. doi: 10.1093/nar/gks590. Epub 2012 Jun 25.
With over one million copies, Alu elements are the most abundant repetitive elements in the human genome. When transcribed, interaction between two Alus that are in opposite orientation gives rise to double-stranded RNA (dsRNA). Although the presence of dsRNA in the cell was previously thought to only occur during viral infection, it is now known that cells express many endogenous small dsRNAs, such as short interfering RNA (siRNAs) and microRNA (miRNAs), which regulate gene expression. It is possible that long dsRNA structures formed from Alu elements influence gene expression. Here, we report that human mRNAs containing inverted Alu elements are present in the mammalian cytoplasm. The presence of these long intramolecular dsRNA structures within 3'-UTRs decreases translational efficiency, and although the structures undergo extensive editing in vivo, the effects on translation are independent of the presence of inosine. As inverted Alus are predicted to reside in >5% of human protein-coding genes, these intramolecular dsRNA structures are important regulators of gene expression.
Alu 元件是人类基因组中最丰富的重复元件，数量超过一百万。当转录时，两个反向取向的 Alu 元件之间的相互作用会产生双链 RNA（dsRNA）。尽管之前人们认为细胞中双链 RNA 的存在仅发生在病毒感染期间，但现在已知细胞表达许多内源性小 dsRNA，如短干扰 RNA（siRNA）和 microRNA（miRNA），它们调节基因表达。可能是来自 Alu 元件的长 dsRNA 结构影响基因表达。在这里，我们报告说，含有反向 Alu 元件的人类 mRNA 存在于哺乳动物细胞质中。这些 3'UTR 内的长分子内 dsRNA 结构会降低翻译效率，尽管这些结构在体内会进行广泛的编辑，但对翻译的影响独立于肌苷的存在。由于预测反向 Alu 存在于 >5%的人类蛋白质编码基因中，因此这些分子内 dsRNA 结构是基因表达的重要调节剂。
