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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Main Authors: Dorota Gudanis, Karolina Zielińska, Daniel Baranowski, Ryszard Kierzek, Piotr Kozłowski, Zofia Gdaniec
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/8/1236
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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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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
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