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Background: Guanine-rich sequences are able to form complex RNA structures termed RNA G-quadruplexes in vitro. Because of their high stability, RNA G-quadruplexes are proposed to exist in vivo and are suggested to be associated with important biological relevance. However, there is a lack of direct evidence for RNA G-quadruplex formation in living eukaryotic cells. Therefore, it is unclear whether any purported functions are associated with the specific sequence content or the formation of an RNA G-quadruplex structure.
Results: Using rG4-seq, we profile the landscape of those guanine-rich regions with the in vitro folding potential in the Arabidopsis transcriptome. We find a global enrichment of RNA G-quadruplexes with two G-quartets whereby the folding potential is strongly influenced by RNA secondary structures. Using in vitro and in vivo RNA chemical structure profiling, we determine that hundreds of RNA G-quadruplex structures are strongly folded in both Arabidopsis and rice, providing direct evidence of RNA G-quadruplex formation in living eukaryotic cells. Subsequent genetic and biochemical analyses show that RNA G-quadruplex folding is able to regulate translation and modulate plant growth.
Conclusions: Our study reveals the existence of RNA G-quadruplex in vivo and indicates that RNA G-quadruplex structures act as important regulators of plant development and growth.
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http://dx.doi.org/10.1186/s13059-020-02142-9 | DOI Listing |
Nucleic Acids Res
September 2025
Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, Brno 61200, Czech Republic.
RNA G-quadruplexes (rG4s) are emerging as vital structural elements involved in processes like gene regulation, translation, and genome stability. Found in untranslated regions of messenger RNAs (mRNAs), they influence translation efficiency and mRNA localization. Additionally, rG4s of long noncoding RNAs and telomeric RNA play roles in RNA processing and cellular aging.
View Article and Find Full Text PDFNucleic Acids Res
August 2025
Department of Chemistry and State Key Laboratory of Marine Environmental Health, City University of Hong Kong, Hong Kong SAR, 000000, China.
TDP-43 is a hallmark protein associated with neurodegenerative diseases. Recent studies revealed TDP-43 as an RNA G-quadruplex (rG4)-binding protein, impacting mRNA transport and function. However, our knowledge of the TDP-43-RNA secondary structure interaction and information on its specific rG4 targets are limited.
View Article and Find Full Text PDFCancer Cell Int
September 2025
Department of Chemical Sciences, University of Naples "Federico II", Via Cintia, 21, Naples, 80126, Italy.
The identification of reliable biomarkers is essential for improving breast cancer (BC) detection, prognosis, and treatment. This study explores a human telomeric G-quadruplex (G4) model, tel, functionalized on Controlled Pore Glass (CPG) support, as a novel biomarker discovery tool. The oligonucleotide tel mimics multimeric G4 structures in telomeric overhangs.
View Article and Find Full Text PDFTalanta
August 2025
School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
G-Quadruplex (G4) DNA structures play a crucial role in regulating various biological processes, rendering them attractive targets for diagnostic and therapeutic applications. The development of G4-targeted fluorescent probes will significantly enhance our understanding of G4 DNA biology in vivo and improve the precision of diagnosing and treating genetic diseases. Herein, we report on a regioisomer of a thiazole orange derivative (SQ2) as a promising fluorescent dye for G4 DNA structures and demonstrate its application in both cell and tumor tissue imaging.
View Article and Find Full Text PDFJ Phys Chem B
September 2025
Department of Physics and Mathematics, Institute of Chemistry, São Paulo State University (UNESP), Araraquara, São Paulo 14800-060, Brazil.
Magnesium ions (Mg) play a crucial role in stabilizing various RNA tertiary motifs, such as pseudoknots, G-quadruplexes, kissing loops, and A-minor motifs, to name a few. Despite their importance, the precise location and role of Mg ions in RNA folding are challenging to characterize both experimentally and computationally. In this study, we employ an all-atom structure-based model integrated with the dynamic counterion condensation (DCC) model to investigate the folding and unfolding transitions of apo SAM-II riboswitch RNA at physiological concentrations of Mg.
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