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

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Date
2012
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Oxford University Press
Abstract
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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double stranded RNA, inosine, messenger RNA, 3' untranslated region, Alu sequence, cell strain HEK293, controlled study, cytoplasm, Gene Expression Regulation, HeLa cell, human, human cell, Lentivirinae, Lentivirus infection, nonhuman, reverse transcription polymerase chain reaction, RNA editing, RNA isolation, RNA structure, RNA translation, Cytoplasm, Gene Expression Regulation, HEK293 Cells, Protein Biosynthesis, RNA, Double-Stranded, RNA, Messenger HEK293 Cells, inosine, 58-63-9
Citation
Capshew, C. R., Dusenbury, K. L., & Hundley, H. A. (2012). Inverted Alu dsRNA structures do not affect localization but can alter translation efficiency of human mRNAs independent of RNA editing. Nucleic Acids Research, 40(17), 8637-8645. http://dx.doi.org/10.1093/nar/gks590
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© 2012 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Article