Abstract
miRNA-Masking Antisense Oligonucleotides Technology (miR-Mask) is an AMO approach of a different sort. A standard miR-Mask is a single-stranded 2′-O-methyl-modified oligoribonucleotide (or other chemically modified), which is a 22-nt antisense to a protein-coding mRNA as a target for an endogenous miRNA of interest. Instead of binding to the target miRNA like an AMO, a miR-Mask does not directly interact with its target miRNA but binds to the binding site of that miRNA in the 3′UTR of the target mRNA by a fully complementary mechanism. In this way, the miR-Mask covers up the access of its target miRNA to the binding site to derepress its target gene (mRNA) via blocking the action of its target miRNA. The anti-miRNA action of a miR-Mask is gene-specific because it is designed to be fully complementary to the target mRNA sequence of a miRNA. The anti-miRNA action of a miR-Mask is also miRNA-specific as well because it is designed to target the binding site of that particular miRNA. The miR-Mask approach is a valuable supplement to the AMO technique; while AMO is indispensable for studying the overall function of a miRNA, the miR-Mask might be more appropriate for studying the specific outcome of regulation of the target gene by the miRNA. This technology was first established by my research group in 2007 [Xiao J, Yang B, Lin H, Lu Y, Luo X, Wang Z, J Cell Physiol 212:285–292, 2007b] and a similar approach with the same concept was subsequently reported by Schier’s laboratory [Choi WY, Giraldez AJ, Schier AF, Science 318:271–274 2007]. Similar to the AMO approach, miR-Mask technology belongs to the “targeting-miRNA” and “miRNA-loss-of-function” strategy.
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References
Choi WY, Giraldez AJ, Schier AF (2007) Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 318:271–274.
Xiao J, Luo X, Lin H, Xu C, Gao H, Wang H, Yang B, Wang Z (2007a) MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts. J Biol Chem 282:12363–12367.
Xiao J, Yang B, Lin H, Lu Y, Luo X, Wang Z (2007b) Novel approaches for gene-specific interference via manipulating actions of microRNAs: Examination on the pacemaker channel genes HCN2 and HCN4. J Cell Physiol 212:285–292.
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© 2009 Springer-Verlag Berlin Heidelberg
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Wang, Z. (2009). miRNA-Masking Antisense Oligonucleotides Technology. In: MicroRNA Interference Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00489-6_10
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DOI: https://doi.org/10.1007/978-3-642-00489-6_10
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