Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation
In this paper, a method to discriminate between two target RNA sequences that differ by one nucleotide only is presented. The method relies on the formation of alternative structures, i.e., quadruplex–duplex hybrid (QDH) and duplex with dangling ends (Dss), after hybridization of DNA or RNA G-rich o...
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2021-08-01
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author | Dorota Gudanis Karolina Zielińska Daniel Baranowski Ryszard Kierzek Piotr Kozłowski Zofia Gdaniec |
author_facet | Dorota Gudanis Karolina Zielińska Daniel Baranowski Ryszard Kierzek Piotr Kozłowski Zofia Gdaniec |
author_sort | Dorota Gudanis |
collection | DOAJ |
description | In this paper, a method to discriminate between two target RNA sequences that differ by one nucleotide only is presented. The method relies on the formation of alternative structures, i.e., quadruplex–duplex hybrid (QDH) and duplex with dangling ends (Dss), after hybridization of DNA or RNA G-rich oligonucleotides with target sequences containing 5′–GGGCUGG–3′ or 5′–GGGCGGG–3′ fragments. Using biophysical methods, we studied the effect of oligonucleotide types (DNA, RNA), non-nucleotide modifications (aliphatic linkers or abasic), and covalently attached G4 ligand on the ability of G-rich oligonucleotides to assemble a G-quadruplex motif. We demonstrated that all examined non-nucleotide modifications could mimic the external loops in the G-quadruplex domain of QDH structures without affecting their stability. Additionally, some modifications, in particular the presence of two abasic residues in the G-rich oligonucleotide, can induce the formation of non-canonical QDH instead of the Dss structure upon hybridization to a target sequence containing the GGGCUGG motif. Our results offer new insight into the sequential requirements for the formation of G-quadruplexes and provide important data on the effects of non-nucleotide modifications on G-quadruplex formation. |
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institution | Directory Open Access Journal |
issn | 2218-273X |
language | English |
last_indexed | 2024-03-10T08:58:30Z |
publishDate | 2021-08-01 |
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spelling | doaj.art-79085307652a44afbc1eac5e7892b4742023-11-22T06:56:47ZengMDPI AGBiomolecules2218-273X2021-08-01118123610.3390/biom11081236Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid FormationDorota Gudanis0Karolina Zielińska1Daniel Baranowski2Ryszard Kierzek3Piotr Kozłowski4Zofia Gdaniec5Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, PolandInstitute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, PolandIn this paper, a method to discriminate between two target RNA sequences that differ by one nucleotide only is presented. The method relies on the formation of alternative structures, i.e., quadruplex–duplex hybrid (QDH) and duplex with dangling ends (Dss), after hybridization of DNA or RNA G-rich oligonucleotides with target sequences containing 5′–GGGCUGG–3′ or 5′–GGGCGGG–3′ fragments. Using biophysical methods, we studied the effect of oligonucleotide types (DNA, RNA), non-nucleotide modifications (aliphatic linkers or abasic), and covalently attached G4 ligand on the ability of G-rich oligonucleotides to assemble a G-quadruplex motif. We demonstrated that all examined non-nucleotide modifications could mimic the external loops in the G-quadruplex domain of QDH structures without affecting their stability. Additionally, some modifications, in particular the presence of two abasic residues in the G-rich oligonucleotide, can induce the formation of non-canonical QDH instead of the Dss structure upon hybridization to a target sequence containing the GGGCUGG motif. Our results offer new insight into the sequential requirements for the formation of G-quadruplexes and provide important data on the effects of non-nucleotide modifications on G-quadruplex formation.https://www.mdpi.com/2218-273X/11/8/1236quadruplex–duplex hybridRNA G-quadruplexesnon-canonical nucleic acid structuresnon-nucleotide chemical modificationsabasicaliphatic linkers |
spellingShingle | Dorota Gudanis Karolina Zielińska Daniel Baranowski Ryszard Kierzek Piotr Kozłowski Zofia Gdaniec Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation Biomolecules quadruplex–duplex hybrid RNA G-quadruplexes non-canonical nucleic acid structures non-nucleotide chemical modifications abasic aliphatic linkers |
title | Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation |
title_full | Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation |
title_fullStr | Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation |
title_full_unstemmed | Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation |
title_short | Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation |
title_sort | impact of a single nucleotide change or non nucleoside modifications in g rich region on the quadruplex duplex hybrid formation |
topic | quadruplex–duplex hybrid RNA G-quadruplexes non-canonical nucleic acid structures non-nucleotide chemical modifications abasic aliphatic linkers |
url | https://www.mdpi.com/2218-273X/11/8/1236 |
work_keys_str_mv | AT dorotagudanis impactofasinglenucleotidechangeornonnucleosidemodificationsingrichregiononthequadruplexduplexhybridformation AT karolinazielinska impactofasinglenucleotidechangeornonnucleosidemodificationsingrichregiononthequadruplexduplexhybridformation AT danielbaranowski impactofasinglenucleotidechangeornonnucleosidemodificationsingrichregiononthequadruplexduplexhybridformation AT ryszardkierzek impactofasinglenucleotidechangeornonnucleosidemodificationsingrichregiononthequadruplexduplexhybridformation AT piotrkozłowski impactofasinglenucleotidechangeornonnucleosidemodificationsingrichregiononthequadruplexduplexhybridformation AT zofiagdaniec impactofasinglenucleotidechangeornonnucleosidemodificationsingrichregiononthequadruplexduplexhybridformation |