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Potent microRNA suppression by RNA Pol II-transcribed 'Tough Decoy' inhibitors.
- Source :
-
RNA (New York, N.Y.) [RNA] 2013 Feb; Vol. 19 (2), pp. 280-93. Date of Electronic Publication: 2012 Dec 18. - Publication Year :
- 2013
-
Abstract
- MicroRNAs (miRNAs) are key regulators of gene expression and modulators of diverse biological pathways. Analyses of miRNA function as well as therapeutic managing of miRNAs rely on cellular administration of miRNA inhibitors which may be achieved by the use of viral vehicles. This study explores the miRNA-suppressive capacity of inhibitors expressed intracellularly from lentivirus-derived gene vectors. Superior activity of two decoy-type inhibitors, a "Bulged Sponge" with eight miRNA recognition sites and a hairpin-shaped "Tough Decoy" containing two miRNA recognition sites, is demonstrated in a side-by-side comparison of seven types of miRNA inhibitors transcribed as short RNAs from an RNA Pol III promoter. We find that lentiviral vectors expressing Tough Decoy inhibitors are less vulnerable than Bulged Sponge-encoding vectors to targeting by the cognate miRNA and less prone, therefore, to reductions in transfer efficiency. Importantly, it is demonstrated that Tough Decoy inhibitors retain their miRNA suppression capacity in the context of longer RNA transcripts expressed from an RNA Pol II promoter. Such RNA Pol II-transcribed Tough Decoy inhibitors are new tools in managing of miRNAs and may have potential for temporal and spatial regulation of miRNA activity as well as for therapeutic targeting of miRNAs that are aberrantly expressed in human disease.
- Subjects :
- Binding Sites
Cell Line, Tumor
Gene Expression
Gene Expression Regulation
Genetic Vectors
Humans
Lentivirus genetics
Luciferases metabolism
MicroRNAs chemistry
Nucleic Acid Conformation
RNA, Messenger analysis
RNA, Messenger metabolism
MicroRNAs antagonists & inhibitors
MicroRNAs genetics
RNA Polymerase II metabolism
RNA, Messenger genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1469-9001
- Volume :
- 19
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- RNA (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 23249752
- Full Text :
- https://doi.org/10.1261/rna.034850.112