MicroRNAs (miRNAs, miRs) are a family of small (19 to 25 nucleotide in length) noncoding RNAs that regulate gene expression by sequence-selective targeting of mRNAs, leading to a translational repression or mRNA degradation, depending on the degree of complementarity between miRNAs and the target sequences. Considering that a single miRNA can target several mRNAs and a single mRNA might contain in the 3’UTR sequence several signals for miRNA recognition, it is calculated that at least 10-40% of human mRNAs are target of microRNAs, leading to the control of highly regulated biological functions, such as differentiation, cell cycle and apoptosis. More in detail, and considering the role of microRNAs, low expression of a given miRNA is expected to be linked with a potential for accumulation of targets mRNAs; conversely, high expression of miRNAs is expected to be causative to low expression of the target mRNAs. Despite the fact that Peptide nucleic acids (PNAs) were proposed for very useful molecules for pharmacological regulation of gene expression in a variety of cellular and molecular systems and were found to be excellent candidates for antisense and antigéne therapies, at present very few data are available on the use of PNAs as molecules targeting micro RNAs. In a first work, Fabani et al. (1) electroporated a PNA against miR-122 to human and rat liver cells, demonstrating block of miR-122 activity. Furthermore, Fabani et al. (2) demonstrated the activity in vivo of a PNA against miR-155. More recently our group described a PNA against the micro RNA 210 which (a) is effciently internalized within target cells only if linked to an arginine-rich peptide; (b) strongly inhibits miR-210 activity; (c) deeply alters the expression of raptor and -globin genes. Unlike commercially available antagomiR, which need continous administrations, a single administration of R-pep-PNA-a210 is sufficient to obtain the biological effects. Taken together, these data highligh the potential of PNA for future therapeutic applications as well as for studying microRNA function and predict a significant increase of studies on this issue in the near future.

Peptide Nucleic Acids (PNAs) for alterations of biological activity of micro RNAs

GAMBARI, Roberto
2010

Abstract

MicroRNAs (miRNAs, miRs) are a family of small (19 to 25 nucleotide in length) noncoding RNAs that regulate gene expression by sequence-selective targeting of mRNAs, leading to a translational repression or mRNA degradation, depending on the degree of complementarity between miRNAs and the target sequences. Considering that a single miRNA can target several mRNAs and a single mRNA might contain in the 3’UTR sequence several signals for miRNA recognition, it is calculated that at least 10-40% of human mRNAs are target of microRNAs, leading to the control of highly regulated biological functions, such as differentiation, cell cycle and apoptosis. More in detail, and considering the role of microRNAs, low expression of a given miRNA is expected to be linked with a potential for accumulation of targets mRNAs; conversely, high expression of miRNAs is expected to be causative to low expression of the target mRNAs. Despite the fact that Peptide nucleic acids (PNAs) were proposed for very useful molecules for pharmacological regulation of gene expression in a variety of cellular and molecular systems and were found to be excellent candidates for antisense and antigéne therapies, at present very few data are available on the use of PNAs as molecules targeting micro RNAs. In a first work, Fabani et al. (1) electroporated a PNA against miR-122 to human and rat liver cells, demonstrating block of miR-122 activity. Furthermore, Fabani et al. (2) demonstrated the activity in vivo of a PNA against miR-155. More recently our group described a PNA against the micro RNA 210 which (a) is effciently internalized within target cells only if linked to an arginine-rich peptide; (b) strongly inhibits miR-210 activity; (c) deeply alters the expression of raptor and -globin genes. Unlike commercially available antagomiR, which need continous administrations, a single administration of R-pep-PNA-a210 is sufficient to obtain the biological effects. Taken together, these data highligh the potential of PNA for future therapeutic applications as well as for studying microRNA function and predict a significant increase of studies on this issue in the near future.
2010
Gambari, Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1404669
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