Inverted Alu dsRNA structures do not affect localization but can alter translation efficiency of human mRNAs independent of RNA editing.

Inverted Alu dsRNA structures do not affect localization but can alter translation efficiency of human mRNAs independent of RNA editing.
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DOI:
10.1093/nar/gks590
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发表时间:
2012-09-01
影响因子:
14.9
通讯作者:
Hundley HA
Hundley HA
中科院分区:
生物学2区
文献类型:
--
作者:
Capshew CR;Dusenbury KL;Hundley HA

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Alu元件是人类基因组中最丰富的重复元件,其拷贝数超过100万。当转录时,处于相反方向的两个Alus之间的相互作用产生双链RNA(dsRNA)。虽然以前认为细胞中dsRNA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),其调节基因表达。由Alu元件形成的长dsRNA结构可能影响基因表达。在这里,我们报告说,人类的mRNA含有倒Alu元素存在于哺乳动物细胞质中。这些长的分子内dsRNA结构在3′-UTR内的存在降低了翻译效率,尽管这些结构在体内经历了广泛的编辑,但对翻译的影响与肌苷的存在无关。由于预测反向Alus存在于>5%的人类蛋白质编码基因中,这些分子内dsRNA结构是基因表达的重要调节因子。
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.
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