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Book ; Online: Impacts of Molecular Structure on Nucleic Acid-Protein Interactions

Brazda, Vaclav / Bowater, Richard

2023

Keywords	Technology: general issues ; Biotechnology ; DNA ; RNA ; protein binding ; G-quadruplex ; triplex ; i-motif ; Z-DNA ; Z-RNA ; cruciform ; amino acid composition ; COVID-19 ; SARS-CoV-2 ; coronavirus ; CNBP ; virus ; bioinformatics ; coevolution ; host ; dsDNA ; G4Hunter ; evolution ; plant science ; nucleic acids ; circular dichroism ; UV light ; ligand ; rhodamine ; thiazole orange ; thioflavin T ; p53 ; aging ; longevity ; comparative analysis ; protein sequence ; Drosophila ; polytene chromosomes ; Canton-S ; agnostic ; ectopic pairing ; 1.688 repeats ; 372-bp repeats ; fragile X-associated primary ovarian insufficiency (FXPOI) ; fragile X-associated tremor/ataxia syndrome (FXTAS) ; fragile X syndrome (FXS) ; repeat instability ; repeat expansion ; chromosome fragility ; RNA gain-of-function ; repeat-associated non-AUG (RAN) translation ; repeat-mediated gene silencing ; Zα domain ; orthogonal representation ; algorithm ; toehold switch ; arithmetic operation ; RNA-RNA interaction ; molecular computing ; reversible computing ; DNA base sequence ; DNA structure ; DNA supercoiling ; epigenetics ; genome stability ; inverted repeat ; replication ; transcription ; nucleic acid-protein interactions
Language	English
Size	1 electronic resource (216 pages)
Publisher	MDPI - Multidisciplinary Digital Publishing Institute
Publishing place	Basel
Document type	Book ; Online
Note	English
HBZ-ID	HT030378192
ISBN	9783036574448 ; 3036574441
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication?

Bidula, Stefan / Brázda, Václav

Genes

2023 Volume 14, Issue 1

Abstract: Non-B nucleic acids structures have arisen as key contributors to genetic variation in SARS-CoV-2. Herein, we investigated the presence of defining spike protein mutations falling within inverted repeats (IRs) for 18 SARS-CoV-2 variants, discussed the ... ...

Abstract	Non-B nucleic acids structures have arisen as key contributors to genetic variation in SARS-CoV-2. Herein, we investigated the presence of defining spike protein mutations falling within inverted repeats (IRs) for 18 SARS-CoV-2 variants, discussed the potential roles of G-quadruplexes (G4s) in SARS-CoV-2 biology, and identified potential pseudoknots within the SARS-CoV-2 genome. Surprisingly, there was a large variation in the number of defining spike protein mutations arising within IRs between variants and these were more likely to occur in the stem region of the predicted hairpin stem-loop secondary structure. Notably, mutations implicated in ACE2 binding and propagation (e.g., ΔH69/V70, N501Y, and D614G) were likely to occur within IRs, whilst mutations involved in antibody neutralization and reduced vaccine efficacy (e.g., T19R, ΔE156, ΔF157, R158G, and G446S) were rarely found within IRs. We also predicted that RNA pseudoknots could predominantly be found within, or next to, 29 mutations found in the SARS-CoV-2 spike protein. Finally, the Omicron variants BA.2, BA.4, BA.5, BA.2.12.1, and BA.2.75 appear to have lost two of the predicted G4-forming sequences found in other variants. These were found in
MeSH term(s)	Humans ; Spike Glycoprotein, Coronavirus/genetics ; Nucleic Acids ; SARS-CoV-2/genetics ; COVID-19/genetics ; Genomics ; 3' Untranslated Regions
Chemical Substances	spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Nucleic Acids ; 3' Untranslated Regions
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14010157
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Quadruplexes and aging: G4-binding proteins regulate the presence of miRNA in small extracellular vesicles (sEVs).

Brázda, Václav / Mergny, Jean-Louis

Biochimie

2023 Volume 214, Issue Pt A, Page(s) 69–72

Abstract: The interaction between proteins and nucleic acids is a core element of life. Many proteins bind nucleic acids via a sequence-specific manner, but there are also many types of proteins that recognize various structural motifs. Researchers have recently ... ...

Abstract	The interaction between proteins and nucleic acids is a core element of life. Many proteins bind nucleic acids via a sequence-specific manner, but there are also many types of proteins that recognize various structural motifs. Researchers have recently found that proteins that can recognize DNA and RNA G-quadruplexes (G4s) are very important for basic cellular processes, particularly in eukaryotes. Some of these proteins are located outside the nucleus and interact with RNA, potentially affecting miRNA functions in intercellular communication, which is facilitated by small extracellular vesicles (sEVs). Imbalances in the production of sEVs are associated with various pathologies and senescence in humans. The distribution of miRNA into sEVs is regulated by two RNA-binding proteins, Alyref and FUS. Both proteins possess G-rich recognition motifs that are compatible with the formation of RNA parallel G4 structures. This lends credence to the new hypothesis that G4-formation in RNAs and their interaction with G4-binding proteins can affect the fate of miRNAs and control their distribution in sEVs that are associated with senescence and aging.
MeSH term(s)	Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Carrier Proteins/genetics ; G-Quadruplexes ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Aging
Chemical Substances	MicroRNAs ; Carrier Proteins
Language	English
Publishing date	2023-01-20
Publishing country	France
Document type	Journal Article
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2023.01.014
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Article ; Online: Abundance of G-Quadruplex Forming Sequences in the Hepatitis Delta Virus Genomes.

Brázda, Václav / Valková, Natália / Dobrovolná, Michaela / Mergny, Jean-Louis

ACS omega

2024 Volume 9, Issue 3, Page(s) 4096–4101

Abstract: Hepatitis delta virus (HDV) is a highly unusual RNA satellite virus that depends on the presence of hepatitis B virus (HBV) to be infectious. Its compact and variable single-stranded RNA genome consists of eight major genotypes distributed unevenly ... ...

Abstract	Hepatitis delta virus (HDV) is a highly unusual RNA satellite virus that depends on the presence of hepatitis B virus (HBV) to be infectious. Its compact and variable single-stranded RNA genome consists of eight major genotypes distributed unevenly across different continents. The significance of noncanonical secondary structures such as G-quadruplexes (G4s) is increasingly recognized at the DNA and RNA levels, particularly for transcription, replication, and translation. G4s are formed from guanine-rich sequences and have been identified in the vast majority of viral, eukaryotic, and prokaryotic genomes. In this study, we analyzed the G4 propensity of HDV genomes by using G4Hunter. Unlike HBV, which has a G4 density similar to that of the human genome, HDV displays a significantly higher number of potential quadruplex-forming sequences (PQS), with a density more than four times greater than that of the human genome. This finding suggests a critical role for G4s in HDV, especially given that the PQS regions are conserved across HDV genotypes. Furthermore, the prevalence of G4-forming sequences may represent a promising target for therapeutic interventions to control HDV replication.
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.3c09288
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dual mode of IFI16 binding to supercoiled and linear DNA: A closer insight.

Valková, Natália / Kratochvilová, Libuše / Martinková, Lucia / Brázda, Václav

Biochemical and biophysical research communications

2023 Volume 667, Page(s) 89–94

Abstract: IFI16 (Interferon inducible protein 16) is a DNA sensor responsible for innate immune response stimulation and a direct viral restriction by modulating gene expression and replication. Many IFI16-DNA binding properties were described - length-dependent ... ...

Abstract	IFI16 (Interferon inducible protein 16) is a DNA sensor responsible for innate immune response stimulation and a direct viral restriction by modulating gene expression and replication. Many IFI16-DNA binding properties were described - length-dependent and sequence-independent binding, oligomerization of IFI16 upon recognition, sliding on the DNA, and preference for supercoiled DNA. However, the question of the role of IFI16-DNA binding in distinct IFI16 functions remains unclear. Here we demonstrate two modes of IFI16 binding to DNA using atomic force microscopy and electrophoretic mobility shift assays. In our study, we show that IFI16 can bind to DNA in the form of globular complexes or oligomers depending on DNA topology and molar ratios. The stability of the complexes is different in higher salt concentrations. In addition, we observed no preferential binding with the HIN-A or HIN-B domains to supercoiled DNA, revealing the importance of the whole protein for this specificity. These results provide more profound insight into IFI16-DNA interactions and may be important in answering the question of self- and non-self-DNA binding by the IFI16 protein and potentially could shed light on the role of DNA binding in distinct IFI16 functions.
MeSH term(s)	DNA, Superhelical ; DNA/metabolism ; Phosphoproteins/metabolism ; Immunity, Innate
Chemical Substances	DNA, Superhelical ; DNA (9007-49-2) ; Phosphoproteins
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.05.049
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Article ; Online: Impacts of Molecular Structure on Nucleic Acid–Protein Interactions

Richard P. Bowater / Václav Brázda

International Journal of Molecular Sciences, Vol 24, Iss 1, p

2022 Volume 407

Abstract: Interactions between nucleic acids and proteins are some of the most important interactions in biology because they are the cornerstones for fundamental biological processes, such as replication, transcription, and recombination [.] ...

Abstract	Interactions between nucleic acids and proteins are some of the most important interactions in biology because they are the cornerstones for fundamental biological processes, such as replication, transcription, and recombination [.]
Keywords	cruciform ; DNA base sequence ; DNA structure ; G-quadruplex ; nucleic acid–protein interactions ; Z-DNA ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genomic Analysis of Non-B Nucleic Acids Structures in SARS-CoV-2: Potential Key Roles for These Structures in Mutability, Translation, and Replication?

Bidula, Stefan / Brázda, Václav

Genes (Basel). 2023 Jan. 06, v. 14, no. 1

2023

Abstract	Non-B nucleic acids structures have arisen as key contributors to genetic variation in SARS-CoV-2. Herein, we investigated the presence of defining spike protein mutations falling within inverted repeats (IRs) for 18 SARS-CoV-2 variants, discussed the potential roles of G-quadruplexes (G4s) in SARS-CoV-2 biology, and identified potential pseudoknots within the SARS-CoV-2 genome. Surprisingly, there was a large variation in the number of defining spike protein mutations arising within IRs between variants and these were more likely to occur in the stem region of the predicted hairpin stem-loop secondary structure. Notably, mutations implicated in ACE2 binding and propagation (e.g., ΔH69/V70, N501Y, and D614G) were likely to occur within IRs, whilst mutations involved in antibody neutralization and reduced vaccine efficacy (e.g., T19R, ΔE156, ΔF157, R158G, and G446S) were rarely found within IRs. We also predicted that RNA pseudoknots could predominantly be found within, or next to, 29 mutations found in the SARS-CoV-2 spike protein. Finally, the Omicron variants BA.2, BA.4, BA.5, BA.2.12.1, and BA.2.75 appear to have lost two of the predicted G4-forming sequences found in other variants. These were found in nsp2 and the sequence complementary to the conserved stem-loop II-like motif (S2M) in the 3′ untranslated region (UTR). Taken together, non-B nucleic acids structures likely play an integral role in SARS-CoV-2 evolution and genetic diversity.
Keywords	RNA ; Severe acute respiratory syndrome coronavirus 2 ; antibodies ; evolution ; genetic variation ; genome ; genomics ; neutralization ; vaccines
Language	English
Dates of publication	2023-0106
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14010157
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: G-quadruplexes in the evolution of hepatitis B virus.

Brázda, Václav / Dobrovolná, Michaela / Bohálová, Natália / Mergny, Jean-Louis

Nucleic acids research

2023 Volume 51, Issue 14, Page(s) 7198–7204

Abstract: Hepatitis B virus (HBV) is one of the most dangerous human pathogenic viruses found in all corners of the world. Recent sequencing of ancient HBV viruses revealed that these viruses have accompanied humanity for several millenia. As G-quadruplexes are ... ...

Abstract	Hepatitis B virus (HBV) is one of the most dangerous human pathogenic viruses found in all corners of the world. Recent sequencing of ancient HBV viruses revealed that these viruses have accompanied humanity for several millenia. As G-quadruplexes are considered to be potential therapeutic targets in virology, we examined G-quadruplex-forming sequences (PQS) in modern and ancient HBV genomes. Our analyses showed the presence of PQS in all 232 tested HBV genomes, with a total number of 1258 motifs and an average frequency of 1.69 PQS per kbp. Notably, the PQS with the highest G4Hunter score in the reference genome is the most highly conserved. Interestingly, the density of PQS motifs is lower in ancient HBV genomes than in their modern counterparts (1.5 and 1.9/kb, respectively). This modern frequency of 1.90 is very close to the PQS frequency of the human genome (1.93) using identical parameters. This indicates that the PQS content in HBV increased over time to become closer to the PQS frequency in the human genome. No statistically significant differences were found between PQS densities in HBV lineages found in different continents. These results, which constitute the first paleogenomics analysis of G4 propensity, are in agreement with our hypothesis that, for viruses causing chronic infections, their PQS frequencies tend to converge evolutionarily with those of their hosts, as a kind of 'genetic camouflage' to both hijack host cell transcriptional regulatory systems and to avoid recognition as foreign material.
MeSH term(s)	Humans ; G-Quadruplexes ; Genome, Human ; Genomics ; Hepatitis B virus/genetics ; Paleontology ; Biological Evolution
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkad556
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Article ; Online: Interaction of Proteins with Inverted Repeats and Cruciform Structures in Nucleic Acids.

Bowater, Richard P / Bohálová, Natália / Brázda, Václav

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract: Cruciforms occur when inverted repeat sequences in double-stranded DNA adopt intra-strand hairpins on opposing strands. Biophysical and molecular studies of these structures confirm their characterization as four-way junctions and have demonstrated that ... ...

Abstract	Cruciforms occur when inverted repeat sequences in double-stranded DNA adopt intra-strand hairpins on opposing strands. Biophysical and molecular studies of these structures confirm their characterization as four-way junctions and have demonstrated that several factors influence their stability, including overall chromatin structure and DNA supercoiling. Here, we review our understanding of processes that influence the formation and stability of cruciforms in genomes, covering the range of sequences shown to have biological significance. It is challenging to accurately sequence repetitive DNA sequences, but recent advances in sequencing methods have deepened understanding about the amounts of inverted repeats in genomes from all forms of life. We highlight that, in the majority of genomes, inverted repeats are present in higher numbers than is expected from a random occurrence. It is, therefore, becoming clear that inverted repeats play important roles in regulating many aspects of DNA metabolism, including replication, gene expression, and recombination. Cruciforms are targets for many architectural and regulatory proteins, including topoisomerases, p53, Rif1, and others. Notably, some of these proteins can induce the formation of cruciform structures when they bind to DNA. Inverted repeat sequences also influence the evolution of genomes, and growing evidence highlights their significance in several human diseases, suggesting that the inverted repeat sequences and/or DNA cruciforms could be useful therapeutic targets in some cases.
MeSH term(s)	DNA/genetics ; DNA, Cruciform ; Humans ; Inverted Repeat Sequences ; Nucleic Acid Conformation ; Nucleic Acids ; Repetitive Sequences, Nucleic Acid/genetics
Chemical Substances	DNA, Cruciform ; Nucleic Acids ; DNA (9007-49-2)
Language	English
Publishing date	2022-05-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23116171
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: New telomere to telomere assembly of human chromosome 8 reveals a previous underestimation of G-quadruplex forming sequences and inverted repeats

Brázda, Václav / Bohálová, Natália / Bowater, Richard P.

Gene. 2022 Feb. 05, v. 810

2022

Abstract: Taking advantage of evolving and improving sequencing methods, human chromosome 8 is now available as a gapless, end-to-end assembly. Thanks to advances in long-read sequencing technologies, its centromere, telomeres, duplicated gene families and repeat- ... ...

Abstract	Taking advantage of evolving and improving sequencing methods, human chromosome 8 is now available as a gapless, end-to-end assembly. Thanks to advances in long-read sequencing technologies, its centromere, telomeres, duplicated gene families and repeat-rich regions are now fully sequenced. We were interested to assess if the new assembly altered our understanding of the potential impact of non-B DNA structures within this completed chromosome sequence. It has been shown that non-B secondary structures, such as G-quadruplexes, hairpins and cruciforms, have important regulatory functions and potential as targeted therapeutics. Therefore, we analysed the presence of putative G-quadruplex forming sequences and inverted repeats in the current human reference genome (GRCh38) and in the new end-to-end assembly of chromosome 8. The comparison revealed that the new assembly contains significantly more inverted repeats and G-quadruplex forming sequences compared to the current reference sequence. This observation can be explained by improved accuracy of the new sequencing methods, particularly in regions that contain extensive repeats of bases, as is preferred by many non-B DNA structures. These results show a significant underestimation of the prevalence of non-B DNA secondary structure in previous assembly versions of the human genome and point to their importance being not fully appreciated. We anticipate that similar observations will occur as the improved sequencing technologies fill in gaps across the genomes of humans and other organisms.
Keywords	DNA ; centromeres ; genes ; humans ; telomeres ; therapeutics
Language	English
Dates of publication	2022-0205
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.146058
Database	NAL-Catalogue (AGRICOLA)

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