Abstract
The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.
Highlights
The microRNAs are small (19−25 nucleotides in length) non-coding RNAs, which have emerged as a fundamental class of potent regulatory molecules [1]
Considering the therapeutic potential of miR-9 and the advantages of peptide nucleic acids (PNAs)-based approaches, in this study we aim to investigate the ability of a PNA designed to target miR-9 to inhibit its function in vivo, using C. intestinalis as a model organism [22]
We explored miR-9 involvement in the C. intestinalis development, performing knockdown experiments with antisense peptide nucleic acids (PNAs)
Summary
The microRNAs (miRNAs) are small (19−25 nucleotides in length) non-coding RNAs, which have emerged as a fundamental class of potent regulatory molecules [1] They are involved in many developmental and physiological processes [2], as well as in pathological conditions. Huge advances have been made in miRNA-based therapy, the in vivo stability of miRNA analogues is still one of the main challenges in this field [5,6]. In this regard, peptide nucleic acids (PNAs) are promising tools for interference with miRNA activities and restoration of normal expression of their targets [7,8]. A set of unique features, including high specific and selective binding affinity towards complementary DNA and RNA strands [11] and enzymatic resistance [12], makes PNAs suitable for antisense therapy [13]
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