Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids

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.

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Hydroxyproline-Based DNA Mimics: A Review on Synthesis and Properties

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20060929 ◽

2006 ◽

Vol 71 (7) ◽

pp. 929-955 ◽

Cited By ~ 10

Author(s):

Vladimir A. Efimov ◽

Oksana G. Chakhmakhcheva

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Phosphonic Acid ◽

Peptide Nucleic Acids ◽

Biological Properties ◽

High Potential ◽

Physicochemical And Biological Properties

With the aim to improve physicochemical and biological properties of natural oligonucleotides, many types of DNA analogues and mimics are designed on the basis of hydroxyproline and its derivatives, and their properties are evaluated. Among them, two types of DNA mimics representing hetero-oligomers constructed from alternating monomers of phosphono peptide nucleic acids and monomers on the base of trans-1-acetyl-4-hydroxy-L-proline (HypNA-pPNAs) and oligomers constructed from monomers containing (2S,4R)-1-acetyl-4-hydroxypyrrolidine-2-phosphonic acid backbone (pHypNAs) are of particular interest. In a set of in vitro and in vivo assays, it was shown that HypNA-pPNAs and pHypNAs demonstrated a high potential for the use in nucleic acid based diagnostics, isolation of nucleic acids and antisense experiments. A review with 53 references.

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miR-7 Knockdown by Peptide Nucleic Acids in the Ascidian Ciona intestinalis

International Journal of Molecular Sciences ◽

10.3390/ijms20205127 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5127 ◽

Cited By ~ 3

Author(s):

Silvia Mercurio ◽

Silvia Cauteruccio ◽

Raoul Manenti ◽

Simona Candiani ◽

Giorgio Scarì ◽

...

Keyword(s):

Nucleic Acids ◽

High Efficiency ◽

Marine Invertebrates ◽

Peptide Nucleic Acids ◽

Ciona Intestinalis ◽

Experimental Models ◽

Sequence Specificity ◽

Antisense Molecule ◽

Ascidian Embryos

Peptide Nucleic Acids (PNAs) are synthetic mimics of natural oligonucleotides, which bind complementary DNA/RNA strands with high sequence specificity. They display numerous advantages, but in vivo applications are still rare. One of the main drawbacks of PNAs application is the poor cellular uptake that could be overcome by using experimental models, in which microinjection techniques allow direct delivery of molecules into eggs. Thus, in this communication, we investigated PNAs efficiency in miR-7 downregulation and compared its effects with those obtained with the commercially available antisense molecule, Antagomir (Dharmacon) in the ascidian Ciona intestinalis. Ascidians are marine invertebrates closely related to vertebrates, in which PNA techniques have not been applied yet. Our results suggested that anti-miR-7 PNAs were able to reach their specific targets in the developing ascidian embryos with high efficiency, as the same effects were obtained with both PNA and Antagomir. To the best of our knowledge, this is the first evidence that unmodified PNAs can be applied in in vivo knockdown strategies when directly injected into eggs.

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Molecular insights on the dynamic stability of peptide nucleic acid functionalized carbon and boron nitride nanotubes

Physical Chemistry Chemical Physics ◽

10.1039/d0cp05759b ◽

2021 ◽

Vol 23 (1) ◽

pp. 219-228

Author(s):

Nabanita Saikia ◽

Mohamed Taha ◽

Ravindra Pandey

Keyword(s):

Nucleic Acid ◽

Boron Nitride ◽

Nucleic Acids ◽

Dynamic Stability ◽

Peptide Nucleic Acid ◽

Rational Design ◽

Peptide Nucleic Acids ◽

Boron Nitride Nanotubes ◽

Molecular Hybrids ◽

Single Wall Nanotubes

The rational design of self-assembled nanobio-molecular hybrids of peptide nucleic acids with single-wall nanotubes rely on understanding how biomolecules recognize and mediate intermolecular interactions with the nanomaterial's surface.

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Application strategies of peptide nucleic acids toward electrochemical nucleic acid sensors

The Analyst ◽

10.1039/d1an00765c ◽

2021 ◽

Author(s):

Qingteng Lai ◽

Wei Chen ◽

Yanke Zhang ◽

Zheng-Chun Liu

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Peptide Nucleic Acids ◽

Dna Probes ◽

Highly Sensitive ◽

Increased Sensitivity ◽

Acid Sensors

Peptide nucleic acids (PNAs) have attracted tremendous interest in the fabrication of highly sensitive electrochemical nucleic acid biosensor due to their higher stability and increased sensitivity than common DNA probes....

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Peptide Nucleic Acids: Applications in Biomedical Sciences

Molecules ◽

10.3390/molecules25153317 ◽

2020 ◽

Vol 25 (15) ◽

pp. 3317

Author(s):

Eylon Yavin

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Peptide Nucleic Acid ◽

Peptide Nucleic Acids ◽

Biomedical Sciences

The DNA mimic, PNA (peptide nucleic acid), has been with us now for almost 3 decades [...]

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Altering behavioral responses and dopamine transporter protein with antisense peptide nucleic acids 1 1Abbreviations: DAT, dopamine transporter; and PNA, peptide nucleic acid.

Biochemical Pharmacology ◽

10.1016/s0006-2952(01)00698-0 ◽

2001 ◽

Vol 62 (7) ◽

pp. 929-932 ◽

Cited By ~ 10

Author(s):

Beth M Tyler-McMahon ◽

Jennifer A Stewart ◽

Joshua Jackson ◽

M.D Bitner ◽

Abdul Fauq ◽

...

Keyword(s):

Nucleic Acid ◽

Nucleic Acids ◽

Dopamine Transporter ◽

Peptide Nucleic Acid ◽

Peptide Nucleic Acids ◽

Behavioral Responses ◽

Transporter Protein ◽

Antisense Peptide

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Role of long-chain acyl-CoAs in the regulation of mycolic acid biosynthesis in mycobacteria

Open Biology ◽

10.1098/rsob.170087 ◽

2017 ◽

Vol 7 (7) ◽

pp. 170087 ◽

Cited By ~ 10

Author(s):

Yi Ting Tsai ◽

Valentina Salzman ◽

Matías Cabruja ◽

Gabriela Gago ◽

Hugo Gramajo

Keyword(s):

Cell Envelope ◽

Phospholipid Composition ◽

Mycolic Acid ◽

Transcriptional Level ◽

Direct Role ◽

Conditional Mutant ◽

In The Wild ◽

Fas Ii

One of the dominant features of the biology of Mycobacterium tuberculosis , and other mycobacteria, is the mycobacterial cell envelope with its exceptional complex composition. Mycolic acids are major and very specific components of the cell envelope and play a key role in its architecture and impermeability. Biosynthesis of mycolic acid (MA) precursors requires two types of fatty acid synthases, FAS I and FAS II, which should work in concert in order to keep lipid homeostasis tightly regulated. Both FAS systems are regulated at their transcriptional level by specific regulatory proteins. FasR regulates components of the FAS I system, whereas MabR and FadR regulate components of the FAS II system. In this article, by constructing a tight mabR conditional mutant in Mycobacterium smegmatis mc 2 155, we demonstrated that sub-physiological levels of MabR lead to a downregulation of the fasII genes, inferring that this protein is a transcriptional activator of the FAS II system. In vivo labelling experiments and lipidomic studies carried out in the wild-type and the mabR conditional mutant demonstrated that under conditions of reduced levels of MabR, there is a clear inhibition of biosynthesis of MAs, with a concomitant change in their relative composition, and of other MA-containing molecules. These studies also demonstrated a change in the phospholipid composition of the membrane of the mutant strain, with a significant increase of phosphatidylinositol. Gel shift assays carried out with MabR and P fasII as a probe in the presence of different chain-length acyl-CoAs strongly suggest that molecules longer than C 18 can be sensed by MabR to modulate its affinity for the operator sequences that it recognizes, and in that way switch on or off the MabR-dependent promoter. Finally, we demonstrated the direct role of MabR in the upregulation of the fasII operon genes after isoniazid treatment.

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