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This report is written by MaltSci based on the latest literature and research findings

What is the role of nucleic acid structures in gene regulation? ​

Abstract ​

Nucleic acids, including DNA and RNA, are fundamental to the storage and expression of genetic information. Recent advances have revealed their complex roles in gene regulation, particularly through their structural diversity and dynamic interactions within the cellular environment. This review explores the multifaceted roles of nucleic acid structures in gene regulation, detailing how their secondary and tertiary formations influence transcriptional and post-transcriptional processes. We provide an overview of the structural characteristics of DNA and RNA, emphasizing the significance of modifications such as 5-methylcytosine, N(6)-methyladenine, and N(6)-methyladenosine in regulating gene expression. The review further delves into the mechanisms of transcriptional regulation, highlighting the importance of nucleosome organization and non-coding RNAs in modulating chromatin accessibility. Additionally, we examine the functional roles of RNA secondary structures and RNA-protein interactions in post-transcriptional regulation, as well as the impact of DNA looping and enhancer-promoter interactions on gene expression. The implications of these nucleic acid structures in disease, particularly in cancer and genetic disorders, are also discussed. Ultimately, this comprehensive examination emphasizes the need for continued research into the roles of nucleic acid structures in gene regulation, with the potential to inform therapeutic strategies targeting these essential biomolecules.

Outline ​

This report will discuss the following questions.

  • 1 Introduction
  • 2 Overview of Nucleic Acid Structures
    • 2.1 Structure of DNA
    • 2.2 Structure of RNA
  • 3 Mechanisms of Gene Regulation by Nucleic Acids
    • 3.1 Transcriptional Regulation
    • 3.2 Post-transcriptional Regulation
  • 4 Functional Roles of RNA Structures in Gene Regulation
    • 4.1 RNA Secondary Structures
    • 4.2 RNA-Protein Interactions
  • 5 The Role of DNA Structures in Gene Regulation
    • 5.1 DNA Looping and Enhancer-Promoter Interactions
    • 5.2 Triplex and Quadruplex Structures
  • 6 Implications of Nucleic Acid Structures in Disease
    • 6.1 Cancer
    • 6.2 Genetic Disorders
  • 7 Conclusion

1 Introduction ​

Nucleic acids, comprising DNA and RNA, are fundamental molecules that serve as the backbone of genetic information in all living organisms. Traditionally recognized for their roles in encoding genetic instructions, recent research has unveiled a more complex involvement of nucleic acids in gene regulation. This expanding understanding highlights the significance of nucleic acid structures, particularly their secondary and tertiary formations, in modulating gene expression. As biological systems increasingly rely on the intricate interplay between nucleic acids and various regulatory factors, the need to explore the multifaceted roles of these structures in gene regulation becomes paramount[1][2].

The significance of studying nucleic acid structures in gene regulation lies not only in their fundamental biological roles but also in their implications for various diseases, including cancer and genetic disorders. Dysregulation of nucleic acid modifications has been correlated with critical biological functions and pathologies, underscoring the necessity of understanding these structures and their modifications in greater depth[2][3]. As researchers continue to uncover the complexities of nucleic acid biology, the implications of these findings extend beyond basic science, influencing therapeutic strategies and our understanding of cellular mechanisms.

Current research indicates that nucleic acids are not merely static carriers of genetic information; they exhibit a remarkable structural diversity that plays vital roles in regulating cellular processes[4]. The dynamic interactions between nucleic acids and proteins, as well as their spatial organization within the nucleus, contribute significantly to gene regulation[5][6]. Moreover, recent advancements in methodologies, such as mass spectrometry, have enhanced our ability to characterize nucleic acid modifications and their functional consequences, revealing layers of complexity previously unrecognized[3].

This review will systematically explore the roles of nucleic acid structures in gene regulation, organized as follows: Section 2 will provide an overview of nucleic acid structures, detailing the distinct features of DNA and RNA. Section 3 will delve into the mechanisms of gene regulation by nucleic acids, encompassing both transcriptional and post-transcriptional regulation. In Section 4, we will focus on the functional roles of RNA structures in gene regulation, particularly emphasizing RNA secondary structures and RNA-protein interactions. Section 5 will discuss the role of DNA structures in gene regulation, including DNA looping, enhancer-promoter interactions, and the significance of triplex and quadruplex formations. Section 6 will highlight the implications of nucleic acid structures in disease, specifically in cancer and genetic disorders. Finally, Section 7 will conclude the review by summarizing the key findings and suggesting directions for future research.

Through this comprehensive examination, we aim to illuminate the intricate network of gene regulation mediated by nucleic acid structures, paving the way for further exploration in this critical area of molecular biology. Understanding these mechanisms is essential for advancing our knowledge of cellular function and developing innovative therapeutic strategies that target nucleic acid structures and their regulatory roles.

2 Overview of Nucleic Acid Structures ​

2.1 Structure of DNA ​

Nucleic acids, primarily DNA and RNA, play pivotal roles in gene regulation through their structural properties and dynamic interactions within the cellular environment. DNA serves as the genetic blueprint, while RNA acts as a messenger and regulator of gene expression. The intricate structures of these nucleic acids are essential for their functions in encoding, transmitting, and regulating genetic information.

The structure of DNA is characterized by its double helix formation, consisting of two strands of nucleotides coiled around each other. Each nucleotide comprises a sugar, a phosphate group, and a nitrogenous base. The specific sequence of these bases encodes genetic information, and the helical structure allows for efficient packing of DNA into chromosomes, facilitating replication and transcription processes necessary for gene expression (Minchin & Lodge, 2019) [7].

Beyond the canonical structure of DNA, various modifications to nucleic acids contribute significantly to gene regulation. Recent research has highlighted the dynamic nature of nucleic acid modifications, which are no longer viewed as static markers but as critical players in cellular processes. For instance, modifications such as 5-methylcytosine (5mC) and N(6)-methyladenine (6mA) in DNA, along with N(6)-methyladenosine (m(6)A) in mRNA, have been shown to influence gene expression and cellular functions. These modifications can stabilize nucleic acid structures, modulate protein translation, and regulate gene expression, linking them to various diseases, including cancers and neurological disorders (Chen et al., 2016; Xie et al., 2024) [2][3].

The spatial organization of nucleic acids within the nucleus also plays a critical role in gene regulation. The formation of nuclear compartments, where DNA, RNA, and proteins are organized, facilitates non-stoichiometric molecular interactions and non-linear regulatory behaviors. These compartments can concentrate regulatory factors and facilitate cooperative interactions, which are essential for precise gene regulation (Bhat et al., 2021) [5].

Furthermore, non-coding RNAs (ncRNAs) and their associated structures, such as paraspeckles, contribute to gene regulation by interacting with regulatory proteins and influencing transcriptional and post-transcriptional processes. The dynamic nature of these structures allows them to adapt to various cellular contexts, further emphasizing the importance of nucleic acid structures in gene regulation (Pisani & Baron, 2019) [6].

In summary, the roles of nucleic acid structures in gene regulation encompass their foundational function in encoding genetic information, the influence of chemical modifications on gene expression, and the spatial organization of nucleic acids within the nucleus. This multifaceted involvement underscores the complexity of gene regulation mechanisms, revealing how structural attributes of nucleic acids are intricately linked to their regulatory roles in biological systems.

2.2 Structure of RNA ​

Nucleic acid structures play a pivotal role in gene regulation through their diverse chemical modifications and intricate spatial organization within the nucleus. Nucleic acids, primarily DNA and RNA, are not merely static carriers of genetic information; they exhibit a range of structural complexities that influence cellular processes, particularly gene expression.

The structure of RNA, for instance, is characterized by its single-stranded nature, allowing it to fold into various three-dimensional shapes. This structural diversity is essential for RNA's functional roles, including messenger RNA (mRNA) processing, translation, and regulation of gene expression. RNA molecules can adopt complex conformations such as G-quadruplexes, which are known to modulate cellular machinery positively or negatively at both DNA and RNA levels. These structures require precise regulation by specific proteins, including helicases, which unwind G-quadruplex formations to maintain cellular homeostasis [8].

In terms of modifications, nucleic acids carry numerous chemical alterations that significantly impact their functionality. Recent studies have highlighted that modifications such as 5-methylcytosine (5mC), N(6)-methyladenine (6mA) in DNA, and N(6)-methyladenosine (m6A), pseudouridine (Ψ), and 5-methylcytidine (m5C) in RNA are crucial for regulating gene expression. These modifications are not static but dynamic, suggesting that nucleic acids can exert critical influences in various cellular processes, particularly in eukaryotic organisms [2].

Moreover, the spatial organization of nucleic acids within the nucleus is integral to gene regulation. The nucleus is compartmentalized into distinct regions that concentrate specific groups of regulatory factors, facilitating non-stoichiometric molecular interactions and non-linear regulatory behaviors. This compartmentalization is essential for the transcription regulation and processing of RNA, as it allows for efficient interactions between nucleic acids and regulatory proteins [5].

Additionally, the formation of nuclear structures such as paraspeckles, which are composed of long non-coding RNAs and RNA-binding proteins, exemplifies the role of RNA in gene regulation. These structures participate in various regulatory pathways and are implicated in numerous pathologies, underscoring the importance of RNA's structural diversity in maintaining cellular function [6].

In summary, nucleic acid structures, particularly RNA, play a multifaceted role in gene regulation through their diverse modifications, complex folding patterns, and spatial organization within the nucleus. These aspects collectively contribute to the dynamic regulation of gene expression, highlighting the intricate interplay between nucleic acid structure and function in biological systems.

3 Mechanisms of Gene Regulation by Nucleic Acids ​

3.1 Transcriptional Regulation ​

Nucleic acid structures play a pivotal role in gene regulation, particularly in the context of transcriptional regulation. The mechanisms underlying this regulation are complex and involve various structural and dynamic aspects of nucleic acids, particularly DNA and RNA.

Transcriptional regulation is fundamentally governed by the accessibility of DNA to transcription factors and RNA polymerase, which is modulated by nucleosome organization. Nucleosomes, as the fundamental units of chromatin, can significantly influence the accessibility of DNA sequences that are crucial for transcriptional regulation. The positioning and organization of nucleosomes around gene promoters and coding regions determine the extent to which transcription factors can bind to their respective sites, thereby affecting gene expression levels. For instance, it has been demonstrated that changes in nucleosome occupancy can lead to transcriptional plasticity, allowing cells to adapt their gene expression profiles in response to various stimuli [9][10].

Furthermore, non-coding RNAs (ncRNAs) have emerged as critical regulators of transcriptional processes by interacting with nucleosome remodeling complexes. These complexes modify chromatin structure, facilitating or hindering the access of transcriptional machinery to DNA. Recent findings suggest that ncRNAs can regulate the activities of nucleosome remodelers, thus influencing the chromatin landscape and, consequently, transcriptional outcomes [11].

The dynamic nature of nucleic acid structures is also crucial in transcriptional regulation. For example, the higher-order structure of chromatin, which includes both nucleosomal and non-nucleosomal components, can impact gene expression by altering chromatin accessibility. Studies have indicated that the structural alterations of chromatin, such as changes in chromatin accessibility during development or cellular differentiation, play a significant role in determining transcriptional outcomes [12].

In summary, nucleic acid structures, particularly through the organization and dynamics of nucleosomes, play a critical role in transcriptional regulation. They determine the accessibility of DNA to transcriptional machinery, mediate interactions with regulatory proteins, and are influenced by various factors including ncRNAs and chromatin remodeling complexes. This intricate interplay highlights the importance of nucleic acid structures in the precise control of gene expression.

3.2 Post-transcriptional Regulation ​

Nucleic acid structures play a pivotal role in the regulation of gene expression, particularly through post-transcriptional mechanisms. These regulatory processes are essential for modulating gene expression at various levels, including mRNA stability, processing, and translation. Post-transcriptional regulation involves complex interactions between RNA molecules and proteins, which collectively determine the fate and function of mRNA transcripts.

One of the primary classes of non-coding RNAs involved in post-transcriptional regulation is small RNAs, including microRNAs (miRNAs), endogenous small interfering RNAs (endo-siRNAs), and PIWI-interacting RNAs (piRNAs). These small RNAs are crucial for the regulation of reproductive tissues and other cellular functions. They exert their effects by binding to target mRNAs, leading to either degradation or inhibition of translation, thereby influencing cellular phenotypes and functions significantly [13].

RNA-binding proteins (RBPs) are also critical players in post-transcriptional regulation. They interact with specific RNA sequences or structures, influencing mRNA stability and translation efficiency. In hematologic cancers, for example, dysregulation of RBPs has been implicated in the pathogenesis of the disease, highlighting their role in maintaining RNA homeostasis [14]. The interaction of RBPs with RNA can lead to mRNA degradation or stabilization, depending on the specific RBP and its binding site on the mRNA [15].

Moreover, long non-coding RNAs (lncRNAs) have emerged as significant regulators of gene expression, impacting chromatin structure and function. These lncRNAs can modulate transcriptional processes and are involved in various cellular functions, suggesting a complex network of regulation that extends beyond traditional coding sequences [16]. The ability of lncRNAs to interact with chromatin and influence gene expression further emphasizes the intricate relationship between nucleic acid structures and gene regulation.

In addition to these RNA classes, post-transcriptional mechanisms are influenced by the spatial organization of RNA within the nucleus. The compartmentalization of RNA molecules into specific nuclear domains, such as transcription factories and nuclear speckles, plays a role in the regulation of transcriptional activity and post-transcriptional RNA processing [17]. This spatial regulation underscores the importance of nuclear architecture in gene expression control.

Overall, the role of nucleic acid structures in gene regulation is multifaceted, encompassing various RNA classes and their interactions with proteins. These interactions govern critical processes such as mRNA stability, translation, and the overall transcriptomic landscape, thereby influencing cellular behavior and contributing to diverse biological functions. The continued exploration of these mechanisms holds promise for understanding gene regulation in health and disease.

4 Functional Roles of RNA Structures in Gene Regulation ​

4.1 RNA Secondary Structures ​

RNA secondary structures play a crucial role in the regulation of gene expression and various cellular processes. The secondary structure of an RNA molecule is integral to its maturation, regulation, and function. It influences gene expression by modulating processes such as transcription, splicing, translation, and RNA stability. For instance, the folding of RNA transcripts into secondary structures via intricate base pairing patterns imparts essential catalytic, ligand-binding, and scaffolding functions to a wide array of RNAs, thereby forming a critical node of biological regulation [18].

Research has shown that RNA secondary structures can regulate post-transcriptional processes by exposing specific sequences or through the formation of structural motifs. This includes sense-antisense double-stranded RNA, hairpin and stem-loop structures, and more complex configurations like bifurcations and pseudoknots [19]. Additionally, specific structural motifs in RNA can influence alternative splicing, which is a vital mechanism for generating protein diversity [20].

High-throughput sequencing and structure-mapping techniques have revealed that the RNA secondary structure is significantly correlated with various epigenetic modifications and mRNA abundance. For example, in Arabidopsis thaliana, it was found that highly unpaired and paired RNAs are strongly associated with euchromatic and heterochromatic epigenetic histone modifications, respectively. This indicates that RNA secondary structure is essential for RNA-mediated post-transcriptional regulatory pathways [21].

Moreover, RNA secondary structures have been shown to affect mRNA translation. The folding of mRNAs can demarcate regions of protein translation and likely influence microRNA-mediated regulation of mRNAs [21]. Additionally, in the context of Plasmodium falciparum, a study highlighted that RNA secondary structure plays a critical role in regulating gene expression, particularly during the parasite's developmental cycles [22].

In mammalian systems, RNA secondary structures are integral to the regulation of gene expression across different cellular compartments. The cytoplasmic structuromes provide insights into how RNA structure connects transcription, translation, and RNA decay [23]. Furthermore, RNA-binding proteins (RBPs) interact with RNA secondary structures to regulate mRNA localization and translation, demonstrating the functional importance of these structures in post-transcriptional regulation [24].

Overall, RNA secondary structures serve as a sophisticated regulatory mechanism in gene expression, influencing various biological processes from transcription to translation, and highlighting their importance in the functional dynamics of RNA molecules in both prokaryotic and eukaryotic systems.

4.2 RNA-Protein Interactions ​

Nucleic acid structures, particularly those of RNA, play pivotal roles in gene regulation through various mechanisms, notably via RNA-protein interactions. These interactions are fundamental to the complexity of gene expression and regulation in eukaryotic cells.

RNA molecules are not merely intermediaries in the flow of genetic information; they actively participate in regulating cellular processes. They engage with other biomolecules, including proteins and other RNA species, thereby influencing gene expression. For instance, structured RNAs such as ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNAs (snRNAs) achieve their functional conformations through intramolecular RNA-RNA interactions, which are critical for their roles in protein synthesis and splicing [25].

Furthermore, RNA-RNA interactions are essential for the biogenesis of various RNA types, including messenger RNAs (mRNAs), microRNAs, and circular RNAs. These interactions can regulate the stability and processing of these molecules, thus impacting gene expression at multiple levels [25]. The advent of high-throughput RNA sequencing technologies has significantly advanced our understanding of the RNA-RNA interactome, revealing thousands of interactions that contribute to the regulation of gene expression [25].

Moreover, RNA structures also play a crucial role in the spatial organization of the nucleus. Recent studies have shown that RNA contributes to the formation of nuclear compartments, which are essential for the regulation of transcription and RNA processing. For example, non-coding RNAs (ncRNAs) are enriched in specific nuclear bodies and are necessary for the establishment and maintenance of these structures. This spatial compartmentalization allows for the concentration of regulatory factors, enhancing the efficiency of gene regulation [26][27].

The dynamic nature of RNA-protein interactions further underscores their importance in gene regulation. Many RNA-binding proteins (RBPs) exhibit a range of affinities for RNA, leading to complex networks of interactions that modulate chromatin structure and transcription factor mobility. For instance, RNAs like NEAT1 and MALAT1 can form high-affinity complexes with RBPs, contributing to the formation of nuclear bodies that regulate gene expression [28].

Additionally, the structural versatility of RNA allows it to act as a scaffold that influences genome organization. RNA can shape chromatin architecture by forming higher-order structures that facilitate long-range interactions within the genome, thereby impacting gene accessibility and transcriptional activity [28].

In summary, nucleic acid structures, particularly RNA, are integral to gene regulation through their interactions with proteins and other RNA molecules. These interactions not only facilitate the processing and stability of RNA but also contribute to the spatial organization of the nucleus, thereby influencing transcriptional regulation and the overall gene expression landscape in eukaryotic cells. The ongoing research in RNA biology continues to reveal the intricate and multifaceted roles of RNA structures in gene regulation, underscoring their significance in cellular function and disease.

5 The Role of DNA Structures in Gene Regulation ​

5.1 DNA Looping and Enhancer-Promoter Interactions ​

Nucleic acid structures play a crucial role in gene regulation, particularly through mechanisms such as DNA looping and enhancer-promoter interactions. Enhancers are specific regulatory DNA sequences that can be located far from the promoters they influence. They contain binding sites for transcription factors and are essential for the recruitment of the transcription machinery to the target promoters. The physical organization of the genome, particularly the formation of chromatin loops, facilitates these long-range interactions between enhancers and promoters.

Research indicates that the three-dimensional (3D) architecture of the genome is vital for enhancer-promoter communication. Enhancer-promoter interactions can be mediated by looping mechanisms that bring distant genomic elements into proximity. For instance, recent evidence suggests that loop extrusion plays a significant role in regulating these interactions, allowing enhancers to dynamically modulate gene expression over large distances [29].

Moreover, the presence of DNA looping is crucial for enhancer-blocking activity. Specific sequence elements can form loops that separate enhancers from their target promoters, effectively blocking the enhancer's function. This mechanism highlights the importance of the spatial arrangement of DNA in regulating gene expression, as the local structural distortion caused by looping is key to this blocking effect [30].

The interplay between enhancer and promoter regions is further complicated by chromatin remodeling, which alters the accessibility of these regions to transcription factors. Various modifications, such as histone changes and ATP-dependent remodeling, can influence how effectively transcription factors can bind to enhancers and promoters, thereby affecting gene expression [31].

Additionally, the role of the nuclear envelope in modulating enhancer-promoter interactions has been recognized. The nuclear envelope can influence the positioning and interactions of enhancers and promoters, linking these processes to developmental regulation and disease states when disrupted [32].

In summary, nucleic acid structures, particularly through the mechanisms of DNA looping and chromatin organization, are fundamental to the regulation of gene expression. These structural dynamics enable precise control over enhancer-promoter interactions, ensuring that genes are expressed at the right time and place in response to various developmental and environmental cues.

5.2 Triplex and Quadruplex Structures ​

Nucleic acid structures, particularly non-canonical forms such as triplexes and quadruplexes, play significant roles in the regulation of gene expression. These structures, which differ from the canonical double helix, are involved in various essential cellular processes, including transcription, translation, and chromatin organization.

G-quadruplexes (G4s) are four-stranded structures formed from guanine-rich sequences found in both DNA and RNA. They are prevalent in key regulatory regions of oncogenes and tumor suppressor genes, thus influencing transcriptional activity. G4s can modulate gene expression by acting as regulatory elements within promoters and untranslated regions, thereby controlling the transcription of associated genes. For instance, they are implicated in the regulation of genes such as c-MYC, k-RAS, and VEGF, which are crucial for cell proliferation and cancer progression (Banerjee et al., 2022; Cree & Kennedy, 2014) [33][34].

The formation and stability of G-quadruplex structures are tightly regulated by various factors, including the presence of specific cations, the local DNA sequence context, and the cellular environment. These structures can affect the binding of transcription factors and other regulatory proteins, thus modulating the transcriptional machinery's access to DNA. Furthermore, G4s are involved in epigenetic regulation, influencing chromatin states and gene expression patterns (Reina & Cavalieri, 2020) [35].

In addition to G-quadruplexes, triplex structures, which consist of three strands of nucleic acids, also contribute to gene regulation. Triplexes can form in regions where there are homopurine or homopyrimidine sequences, allowing for specific binding to target DNA sequences. This binding can interfere with transcription factor access or the progression of RNA polymerase, thus inhibiting or enhancing transcription (Matsumoto & Sugimoto, 2021) [36].

The ability of these non-canonical structures to influence gene expression makes them attractive targets for therapeutic interventions. Small molecules that can stabilize or disrupt these structures have been developed, showing promise in cancer therapy by selectively modulating the expression of oncogenes and other critical regulatory genes (Xiong et al., 2015; Moruno-Manchon et al., 2017) [37][38].

In summary, non-canonical nucleic acid structures such as G-quadruplexes and triplexes are integral to the regulation of gene expression. Their unique properties allow them to serve as regulatory elements that can either promote or inhibit the transcription of genes, thus playing a pivotal role in cellular function and disease progression.

6 Implications of Nucleic Acid Structures in Disease ​

6.1 Cancer ​

Nucleic acid structures play a critical role in gene regulation, particularly in the context of cancer and other diseases. Recent studies have highlighted that non-canonical structures of nucleic acids can significantly influence the expression of genes related to disease, thereby contributing to the onset and progression of various conditions, including cancer and neurodegenerative diseases.

One of the key findings is that transient, non-canonical structural changes in nucleic acids can regulate the expression of disease-related genes. These non-canonical structures are involved in several cellular functions, such as gene expression regulation through transcription and translation, epigenetic regulation of chromatin, and DNA recombination. Specifically, transcripts generated from repeat sequences of neurodegenerative disease-related genes can form non-canonical structures that are implicated in protein transport and the formation of toxic aggregates. This suggests that the structural dynamics of nucleic acids are crucial for cellular processes that may lead to disease [39].

Furthermore, the compartmentalization of nucleic acids and regulatory proteins within nuclear microenvironments is vital for the combinatorial control of gene expression. This subnuclear organization allows for the integration of physiological signals that regulate gene expression, DNA replication, and repair. Changes in nuclear organization are frequently observed in cancer, indicating that the spatial and temporal dynamics of nucleic acid structures can influence tumorigenesis and the overall behavior of cancer cells [40].

The role of microRNAs (miRNAs), a class of non-coding RNAs, further illustrates the regulatory potential of nucleic acid structures in cancer. miRNAs are involved in the regulation of cell growth, differentiation, and apoptosis, providing an additional layer of genetic regulation in tumorigenesis. Their dynamic involvement in gene expression highlights the complexity of nucleic acid functions in cancer [41].

Additionally, engineered systems, such as mesoporous silica nanoparticles, have been developed to deliver nucleic acids effectively for gene therapy in cancer treatment. These systems aim to enhance the stability and delivery of nucleic acids, overcoming biological barriers to achieve targeted gene expression regulation within tumor cells [42].

Overall, the structural diversity and dynamic nature of nucleic acids are essential for understanding their regulatory roles in gene expression, particularly in the context of cancer. These insights not only enhance our understanding of disease mechanisms but also open avenues for novel therapeutic strategies targeting nucleic acid structures in cancer treatment [43].

6.2 Genetic Disorders ​

Nucleic acids, particularly DNA and RNA, play a crucial role in gene regulation through their structural diversity and dynamic behavior. Recent studies have highlighted the importance of non-canonical structures of nucleic acids, which can significantly influence the expression of genes associated with various diseases, including cancer and neurodegenerative disorders. These non-canonical structures, which deviate from the traditional double helix of DNA or standard forms of RNA, can regulate gene expression by affecting transcription and translation processes, as well as epigenetic modifications of chromatin.

For instance, mutations or epigenetic silencing can suppress the expression of tumor suppressor genes, while neurodegenerative disease-related genes may exhibit altered expression due to erroneous protein sequences or the production of toxic peptides from extended repeat transcripts. These alterations are often linked to the structural configurations of nucleic acids that can change in response to environmental factors, thereby regulating the expression of disease-related genes. Such transient structural changes have been shown to influence key cellular functions, including transcription, translation, and even DNA recombination, ultimately impacting disease progression [39].

Moreover, the structural modifications of nucleic acids are not merely passive but actively participate in cellular mechanisms. For example, certain RNA modifications, such as N(6)-methyladenosine (m(6)A), play critical roles in regulating gene expression and are implicated in various pathologies, including cancers and neurological disorders [2]. These modifications can alter the stability of RNA molecules, their translation efficiency, and their interactions with proteins, thereby influencing cellular outcomes.

The interplay between nucleic acid structures and gene regulation is further exemplified by the development of therapeutic strategies targeting these structures. For instance, synthetic peptides have been explored for their ability to specifically bind to disease-related nucleic acids, thereby modulating their function and offering potential therapeutic avenues for genetic disorders [44].

In summary, the structural characteristics of nucleic acids are integral to gene regulation and have significant implications for understanding and treating genetic disorders. The dynamic nature of nucleic acid structures, particularly their ability to form non-canonical configurations, allows them to regulate gene expression in response to various stimuli, thereby influencing the onset and progression of diseases. This understanding paves the way for novel therapeutic approaches aimed at correcting dysregulated gene expression associated with genetic disorders.

7 Conclusion ​

This review highlights the critical roles of nucleic acid structures in gene regulation, emphasizing the intricate interplay between DNA and RNA and their structural modifications. The findings underscore that nucleic acids are not merely passive carriers of genetic information; rather, they exhibit dynamic structural properties that are essential for regulating various cellular processes. The evaluation of current research reveals significant advancements in understanding how nucleosome organization, RNA secondary structures, and non-canonical forms like G-quadruplexes and triplexes contribute to gene expression modulation. Moreover, the implications of these structures in disease contexts, particularly in cancer and genetic disorders, underscore the necessity for further exploration of nucleic acid biology. Future research should focus on elucidating the mechanisms by which nucleic acid structures interact with regulatory proteins and the nuclear architecture to refine our understanding of gene regulation. Additionally, the development of therapeutic strategies targeting these structures could pave the way for innovative treatments in genetic diseases and cancer, highlighting the translational potential of this research area.

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