Thermodynamic Stability of G‐Quadruplexes: Impact of Sequence and Environment

Jana, Jagannath; Weisz, Klaus

doi:10.1002/cbic.202100127

Cited by 42 publications

(22 citation statements)

References 89 publications

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“…Stacking of more than two layers of G-quartet drives the folding of RNA G-quadruplex, with the loops connecting G-tracts outside the stacked G-quartets. Both the number of G-quartet layers and loop length have a profound impact on the thermostability of RG4 (Pandey et al, 2013 ; Kwok and Merrick, 2017 ; Jana and Weisz, 2021 ). The most common RG4s are constituted with two layers of G-quartet (G2-RG4) or three layers of G-quartet (G3-RG4).…”

Section: Intrinsic and Extrinsic Features Affecting Rna G-quadruplex ...mentioning

confidence: 99%

A Key Molecular Regulator, RNA G-Quadruplex and Its Function in Plants

2022

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RNA structure plays key roles in plant growth, development, and adaptation. One of the complex RNA structures is the RNA G-quadruplex (RG4) where guanine-rich sequences are folded into two or more layers of G-quartets. Previous computational predictions of RG4 revealed that it is widespread across the whole transcriptomes in many plant species, raising the hypothesis that RG4 is likely to be an important regulatory motif in plants. Recently, with the advances in both high-throughput sequencing and cell imaging technologies, RG4 can be detected in living cells as well as at the genome-wide scale. Here, we provide a comprehensive review of recent developments in new methods for detecting RG4 in plants. We also summarize the new functions of RG4 in regulating plant growth and development. We then discuss the possible role of RG4 in adapting to environmental conditions along with evolutionary perspectives.

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Section: Intrinsic and Extrinsic Features Affecting Rna G-quadruplex ...mentioning

confidence: 99%

A Key Molecular Regulator, RNA G-Quadruplex and Its Function in Plants

2022

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“…However, loop domains as well as 5′-and 3′-flanking sequences may significantly contribute to the quadruplex stability by tertiary interactions, often forming an additional capping structure on an outer G-tetrad. Capping structures or a dimerization by end-stacking are frequently observed phenomena and particularly important for adding stability to quadruplex scaffolds comprising only two tetrad layers [18].…”

Section: Stability and Polymorphism Of G-quadruplexesmentioning

confidence: 99%

A world beyond double-helical nucleic acids: the structural diversity of tetra-stranded G-quadruplexes

Weisz

2021

ChemTexts

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Nucleic acids can adopt various secondary structures including double-, triple-, and tetra-stranded helices that differ by the specific hydrogen bond mediated pairing pattern between their nucleobase constituents. Whereas double-helical DNA relies on Watson–Crick base pairing to play a prominent role in storing genetic information, G-quadruplexes are tetra-stranded structures that are formed by the association of guanine bases from G-rich DNA and RNA sequences. During the last few decades, G-quadruplexes have attracted considerable interest after the realization that they form and exert regulatory functions in vivo. In addition, quadruplex architectures have also been recognized as versatile and powerful tools in a growing number of technological applications. To appreciate the astonishing structural diversity of these tetra-stranded structures and to give some insight into basic interactions that govern their folding, this article gives an overview of quadruplex structures and rules associated with the formation of different topologies. A brief discussion will also focus on nonconventional quadruplexes as well as on general principles when targeting quadruplexes with ligands. Graphic abstract

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“…The in vitro selection technique named SELEX (Systematic Evolution of Ligands by Exponential Enrichment), a combinatorial method to select aptamers, revealed several highly specific G-quadruplexes forming oligonucleotide aptamers (G4-aptamers) against a variety of protein targets [1,2]. This is not particularly surprising, taking into account that G4 structures are very stable nucleic acid secondary conformations [3]. The folding in G4 conformations requires G-rich sequences that can form quadrangular planar arrangements of four guanosines (known as G-tetrads) connected through eight H-bonds overall.…”

Section: Introductionmentioning

confidence: 99%

Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine

Virgilio

Benigno

Pecoraro

et al. 2021

IJMS

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In this paper, we report our investigations on five T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties.

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Thermodynamic Stability of G‐Quadruplexes: Impact of Sequence and Environment

Cited by 42 publications

References 89 publications

A Key Molecular Regulator, RNA G-Quadruplex and Its Function in Plants

A Key Molecular Regulator, RNA G-Quadruplex and Its Function in Plants

A world beyond double-helical nucleic acids: the structural diversity of tetra-stranded G-quadruplexes

Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine

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