Modulation of the Biological Activity of microRNA‐210 with Peptide Nucleic Acids (PNAs)
Citations Over TimeTop 12% of 2011 papers
Abstract
Herein we describe the activity of a peptide nucleic acid (PNA) that targets microRNA-210 (miR-210), which is associated with hypoxia and is modulated during erythroid differentiation. PNAs directed against miR-210 were designed to bind with high affinity to the target RNA strand and to undergo efficient uptake in target cells. A polyarginine-PNA conjugate directed against miR-210 (Rpep-PNA-a210) showed both very high affinity for RNA and efficient uptake into target cells without the need for transfection reagents. An unmodified PNA of the same sequence displayed the ability to bind RNA, but cellular uptake was very poor. Consistent with this, only Rpep-PNA-a210 strongly inhibited miR-210 activity, as evaluated by assays on undifferentiated K562 cells and on cells treated with mithramycin, which was found to induce erythroid differentiation and miR-210 overexpression. Targeting miR-210 by Rpep-PNA-a210 resulted in: 1) a decrease in miR-210 levels as measured by RT-PCR, 2) up-regulation of raptor mRNA, 3) a decrease in γ-globin mRNA, and 4) decreased expression of differentiated functions (i.e., proportion of benzidine-positive cells, content of embryo-fetal hemoglobins). The efficient delivery of anti-miR PNAs through a suitable peptide carrier (Rpep-PNA-a210) leads to the inhibition of miR-210 activity, altering the expression of miR-210-regulated erythroid functions.
Related Papers
- Photochemistry and the nucleic acids(1990)
- → Study of the Reaction Between the Nucleic Acid and Y-BPMPHD-CTMAB Complex and Its Analytical Application(2004)9 cited
- → Nucleic Acids as Detection Tools(2010)3 cited
- → ChemInform Abstract: Bridged Nucleic Acids: Development, Synthesis and Properties(2010)
- Effect of temperature on soluble protein and nucleic acid of leaves in Chinese Kale(Brassica alboglabra Bailey)(2008)