'If G-quadruplexes form so readily in vitro, Nature will have found a way of using them in vivo' (Statement by Aaron Klug over 30 years ago).During the last decade, four-stranded helical structures called G-quadruplex (or G4) have emerged from being a structural curiosity observed in vitro, to being recognized as a possible nucleic acid based mechanism for regulating multiple biological processes in vivo. The sequencing of many genomes has revealed that they are rich in sequence motifs that have the potential to form G-quadruplexes and that their location is non-random, correlating with functionally important genomic regions. In this short review, we summarize recent evidence for the in vivo presence and function of DNA and RNA G-quadruplexes in various cellular pathways including DNA replication, gene expression and telomere maintenance. We also highlight remaining open questions that will have to be addressed in the future.
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http://dx.doi.org/10.1093/nar/gkv862 | DOI Listing |
Angew Chem Int Ed Engl
January 2025
University of Science and Technology of China, Department of Chemistry, 96 JinZhai Road, 230026, Hefei, CHINA.
Environment-recognizing DNA nanodevices have proven promising for cellular manipulation and disease treatment, whereas how to sequentially respond to different cellular microenvironments remains a challenge. To this end, here we elaborate a logic-gated intelligent DNA nanorobot (Gi-DR) for the cascade response to inter- and intra-cellular microenvironments, thereby achieving lysosome-targeted cargo delivery for subcellular interference and tumor treatment with enhanced efficacy. Utilizing G-quadruplexes to respond to high-level K+ in cancer cell surrounding, this Gi-DR nanorobot can activate an aptamer-based transmembrane DNA machine that delivers molecular payloads to cellular lysosome.
View Article and Find Full Text PDFJ Comput Chem
January 2025
Regional Center of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, Olomouc, Czech Republic.
Doxorubicin (DOX) is a widely used chemotherapeutic agent known for intercalating into DNA. However, the exact modes of DOX interactions with various DNA structures remain unclear. Using molecular dynamics (MD) simulations, we explored DOX interactions with DNA duplexes (dsDNA), G-quadruplex, and nucleosome.
View Article and Find Full Text PDFBiomolecules
January 2025
Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba 305-0047, Japan.
Synthetic cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) are promising candidates for vaccine adjuvants, because they activate immune responses through the Toll-like receptor 9 (TLR9) pathway. However, unmodified CpG ODNs are quickly degraded by serum nucleases, and their negative charge hinders cellular uptake, limiting their clinical application. Our group previously reported that guanine-quadruplex (G4)-forming CpG ODNs exhibit enhanced stability and cellular uptake.
View Article and Find Full Text PDFBiosensors (Basel)
January 2025
School of Pharmacy & Biomolecular Sciences, Faculty of Health, Innovation, Technology and Science, Liverpool John Moores University, Liverpool L3 3AF, UK.
G-quadruplex (G4) DNAzymes with peroxidase activities hold potential for applications in biosensing. While these nanozymes are easy to assemble, they are not as efficient as natural peroxidase enzymes. Several approaches are being used to better understand the structural basis of their reaction mechanisms, with a view to designing constructs with improved catalytic activities.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Max Perutz Labs, Vienna Biocenter Campus, Vienna 1030, Austria.
RNA G-quadruplexes (rG4s), the four-stranded structures formed by guanine-rich RNA sequences, are recognized by regions in RNA-binding proteins (RBPs) that are enriched in arginine-glycine repeats (RGG motifs). Importantly, arginine and glycine are encoded by guanine-rich codons, suggesting that some RGG motifs may both be encoded by and interact with rG4s in autogenous messenger RNAs (mRNAs). By analyzing transcriptome-wide rG4 datasets, we show that hundreds of RGG motifs in humans are at least partly encoded by rG4s, with an increased incidence for longer RGG motifs (~10 or more residues).
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