Insight into RNA G-Quadruplex/Ligand Complex: The Interaction Mechanism and Application in Biosensing DOI
Jie Teng, Lanxin Jiang, Xiaojuan Liu

и другие.

Опубликована: Янв. 1, 2023

G-quadruplexes(G4s) are important non-canonical nucleic acid secondary structures in human genome, whose interaction with their ligands, such as ThT and hemin, have been meticulously studied widely utilized label-free biosensing field. However, the mechanism of G4/ligand complex still needs to be further explored. For example, difference between RNA G4 DNA when possessed same sequence, way improve its signal output performance so build better systems. Here, based on most classic PS2.M sequence chosen model hemin being added a control, we performed series explorations found that fluorescence intensity G4/ThT was about two-fold complex, which opposite G4/hemin complex. And after A base modification, it could even reach three-fold increase. Further, by exploring ThT, deemed bimolecular binding mode, dimerized parallel topology structure well higher affinity contributed excellent ability. free ion conditions, stronger environmental tolerance ability, positive effect successfully used for in-situ imaging BCR-ABL e13a2 e14a2 isoforms. This study demonstrated powerful tool transducing, thus would provide novel solution construction highly sensitive biosensors

Язык: Английский

PET Imaging of Solid Tumors with a G-Quadruplex-Targeting 18F-Labeled Peptide Probe DOI

Xiao‐Chun Guo,

Dazhi Shi,

Shun Huang

и другие.

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Positron emission tomography (PET) is a common imaging technique and can provide accurate information about the size, shape, location of tumors. Recent evidence has shown that G-quadruplex structures (G4s) are identified in human oncogenes, these special recognized as diagnostic cancer markers drug targets for anticancer therapies. Although number techniques vivo G4s have been developed, achieving sufficient sensitivity selectivity remains challenging. Herein, we engineered developed radiolabeled peptide probe [18F]AlF-NOTA-RHAU18 targeting mitochondrial DNA PET imaging. The results study indicate this able to visualize detect solid tumors living homozygous mice. In addition, distribution cells was investigated using FITC-RHAU18. This work may offer new insights into development tools by G4s.

Язык: Английский

Процитировано

1
Polymeric Properties of Telomeric G-Quadruplex Multimers: Effects of Chemically Inert Crowders DOI Creative Commons
Deniz Mostarac,

Mattia Trapella,

Luca Bertini

и другие.

Biomacromolecules, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

G-quadruplexes are noncanonical DNA structures rather ubiquitous in the human genome, which thought to play a crucial role development of majority cancers. Here, we present novel coarse-grained approach modeling that accounts for their structural flexibility. We apply it study polymeric properties G-quadruplex multimers, with and without crowder molecules, mimic vivo conditions. find that, contrary some suggestions found literature, long multimers flexible macromolecules, local persistence length comparable monomer size, exhibiting chain stiffness variation profile consistent real polymer good solvent. Moreover, crowded environment (up 10% volume fraction), report exhibit an increased propensity coiling, corresponding decrease measured stiffness.

Язык: Английский

Процитировано

0
Selective recognition of RNA G-quadruplex in vitro and in cells by L-aptamer–D-oligonucleotide conjugate DOI Creative Commons
Haizhou Zhao, Hill Lam Lau, Kun Zhang

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 52(22), С. 13544 - 13560

Опубликована: Ноя. 18, 2024

Abstract RNA Guanine-quadruplexes (rG4s) are important nucleic acid structures that govern vital biological processes. Although numerous tools have been developed to target rG4s, few specific capable of discerning individual rG4 interest. Herein, we design and synthesize the first L-aptamer–antisense oligonucleotide (ASO) conjugate, L-Apt.4–1c-ASO15nt(APP), with a focus on recognizing amyloid precursor protein (APP) region as an example. The L-aptamer module binds structure, whereas ASO hybridizes flanking sequences. Together, these two modules enhance precise recognition APP rG4. We demonstrate L-Apt.4–1c-ASO15nt(APP) conjugate can interact sub-nanomolar binding affinity, distinguish from other G4s non-G4s in vitro cells. also show inhibit expression. Notably, investigate inhibitory mechanism this newly tool, reveal it controls gene expression by hindering DHX36 unraveling rG4, well promoting translational inhibition RNase H-mediated mRNA knockdown activity. Our novel L-aptamer–ASO tool not only enables interest, but allows efficient control via targeting rG4-containing transcripts

Язык: Английский

Процитировано

1
The transcription of TCOF1 , the main gene associated with Treacher-Collins syndrome, is regulated by G-quadruplexes and Cellular Nucleic acid Binding Protein (CNBP) DOI Creative Commons

Mauco Gil Rosas,

Cielo Centola,

Valeria S. Mouguelar

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 5, 2024

Abstract Treacle ribosome biogenesis factor 1 ( TCOF1 ) is responsible for about 80% of mandibular dysostosis (MD) cases. We have formerly identified a correlation between and CNBP (CCHC-type zinc finger nucleic acid binding protein) expression in human mesenchymal cells. Given the established role gene regulation during rostral development, we explored potential to modulate transcription. Computational analysis sites (CNBP-BSs) promoter revealed several putative sites, two which (Hs791 Hs2160) overlap with G-quadruplex (G4) sequences (PQSs). validated folding these PQSs measuring circular dichroism fluorescence appropriate synthetic oligonucleotides. In vitro studies confirmed purified target (both folded as G4 unfolded) K d values nM range. ChIP assays conducted HeLa cells chromatin detected promoter. Transient transfections HEK293 that Hs2160 cloned upstream SV40 increased transcription downstream firefly luciferase reporter gene. also CNBP-BS PQS (Dr2393) zebrafish orthologue nolc1 ). Disrupting this embryos by microinjecting DNA antisense oligonucleotides complementary Dr2393 reduced recapitulated craniofacial anomalies characteristic Treacher Collins Syndrome. Both cnbp overexpression Morpholino-mediated knockdown induced These results suggest modulates transcriptional through mechanism involving folding/unfolding, active vertebrates distantly related bony fish humans. findings may implications understanding treating MD.

Язык: Английский

Процитировано

0
The transcription of the main gene associated with Treacher–Collins syndrome (TCOF1) is regulated by G-quadruplexes and cellular nucleic acid binding protein (CNBP) DOI Creative Commons

Mauco Gil Rosas,

Cielo Centola,

Mercedes de Torres

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Март 29, 2024

Abstract Treacle ribosome biogenesis factor 1 ( TCOF1 ) is responsible for about 80% of mandibular dysostosis (MD) cases. We have formerly identified a correlation between and CNBP (CCHC-type zinc finger nucleic acid binding protein) expression in human mesenchymal cells. Given the established role gene regulation during rostral development, we explored potential to modulate transcription. Computational analysis sites (CNBP-BSs) promoter revealed several putative sites, two which (Hs791 Hs2160) overlap with G-quadruplex (G4) sequences (PQSs). validated folding these PQSs measuring circular dichroism fluorescence appropriate synthetic oligonucleotides. In vitro studies confirmed purified target (both folded as G4 unfolded) K d values nM range. ChIP assays conducted HeLa cells chromatin detected promoter. Transient transfections HEK293 that Hs2160 cloned upstream SV40 increased transcription downstream firefly luciferase reporter gene. also CNBP-BS PQS (Dr2393) zebrafish orthologue nolc1 ). Disrupting this embryos by microinjecting DNA antisense oligonucleotides complementary Dr2393 reduced recapitulated craniofacial anomalies characteristic Treacher Collins Syndrome. Both cnbp overexpression Morpholino-mediated knockdown induced These results suggest modulates transcriptional through mechanism involving folding/unfolding, active vertebrates distantly related bony fish humans. findings may implications understanding treating MD.

Язык: Английский

Процитировано

0
Insight into RNA G-Quadruplex/Ligand Complex: The Interaction Mechanism and Application in Biosensing DOI
Jie Teng, Lanxin Jiang, Xiaojuan Liu

и другие.

Опубликована: Янв. 1, 2023

G-quadruplexes(G4s) are important non-canonical nucleic acid secondary structures in human genome, whose interaction with their ligands, such as ThT and hemin, have been meticulously studied widely utilized label-free biosensing field. However, the mechanism of G4/ligand complex still needs to be further explored. For example, difference between RNA G4 DNA when possessed same sequence, way improve its signal output performance so build better systems. Here, based on most classic PS2.M sequence chosen model hemin being added a control, we performed series explorations found that fluorescence intensity G4/ThT was about two-fold complex, which opposite G4/hemin complex. And after A base modification, it could even reach three-fold increase. Further, by exploring ThT, deemed bimolecular binding mode, dimerized parallel topology structure well higher affinity contributed excellent ability. free ion conditions, stronger environmental tolerance ability, positive effect successfully used for in-situ imaging BCR-ABL e13a2 e14a2 isoforms. This study demonstrated powerful tool transducing, thus would provide novel solution construction highly sensitive biosensors

Язык: Английский

Процитировано

0