RG1 is a quadruplex-forming sequence in the SARS-CoV-2 genome proposed as possible therapeutic target for COVID-19. We demonstrate that the dominant conformation of RG1 under physiological conditions differs from the parallel quadruplex previously assumed. Through comprehensive investigations employing CD, UV, NMR, DSC, gel electrophoresis, MD simulations, in silico spectroscopy and the use of truncated RG1 sequences, we have identified this stable conformation as an RNA G-triplex composed of two G-triads. We believe this previously unreported RNA structure could serve as a novel therapeutic target. Our findings open new avenues for further studies on the presence and biological role of RNA G-triplexes in vivo.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656141 | PMC |
| http://dx.doi.org/10.1002/anie.202415448 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pre-Defined Stem-Loop Structure Library for the Discovery of L-RNA Aptamers that Target RNA G-Quadruplexes.
Angew Chem Int Ed Engl
October 2024
Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong Kowloon Tong, Hong Kong SAR, China.
L-RNA aptamers have been developed to target G-quadruplexes (G4s) and regulate G4-mediated gene expression. However, the aptamer selection process is laborious and challenging, and aptamer identification is subject to high failure rates. By analyzing the previously reported G4-binding L-RNA aptamers, we found that the stem-loop (SL) structure is favored by G4 binding.
View Article and Find Full Text PDFExperimental and Computational Evidence of a Stable RNA G-Triplex Structure at Physiological Temperature in the SARS-CoV-2 Genome.
Angew Chem Int Ed Engl
December 2024
Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126, Naples, Italy.
RG1 is a quadruplex-forming sequence in the SARS-CoV-2 genome proposed as possible therapeutic target for COVID-19. We demonstrate that the dominant conformation of RG1 under physiological conditions differs from the parallel quadruplex previously assumed. Through comprehensive investigations employing CD, UV, NMR, DSC, gel electrophoresis, MD simulations, in silico spectroscopy and the use of truncated RG1 sequences, we have identified this stable conformation as an RNA G-triplex composed of two G-triads.
View Article and Find Full Text PDFBalancing act: BRCA2's elaborate management of telomere replication through control of G-quadruplex dynamicity.
Bioessays
August 2024
Department of Biological Sciences & Institute of Molecular Biology and Genetics (IMBG), Seoul National University, Seoul, South Korea.
In billion years of evolution, eukaryotes preserved the chromosome ends with arrays of guanine repeats surrounded by thymines and adenines, which can form stacks of four-stranded planar structure known as G-quadruplex (G4). The rationale behind the evolutionary conservation of the G4 structure at the telomere remained elusive. Our recent study has shed light on this matter by revealing that telomere G4 undergoes oscillation between at least two distinct folded conformations.
View Article and Find Full Text PDFInsights into the structural dynamics and helicase-catalyzed unfolding of plant RNA G-quadruplexes.
J Biol Chem
August 2022
State Key Laboratory of Crop Stress Adaptation and Improvement, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, Henan University, Kaifeng, China. Electronic address:
RNA G-quadruplexes (rG4s) are noncanonical RNA secondary structures formed by guanine (G)-rich sequences. These complexes play important regulatory roles in both animals and plants through their structural dynamics and are closely related to human diseases and plant growth, development, and adaption. Thus, studying the structural dynamics of rG4s is fundamentally important; however, their folding pathways and their unfolding by specialized helicases are not well understood.
View Article and Find Full Text PDFTelomere G-triplex lights up Thioflavin T for RNA detection: new wine in an old bottle.
Anal Bioanal Chem
August 2022
State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology - Wuhan National Laboratory for Optoelectronics, Chinese Academy of Sciences, Wuhan, 430071, China.
Few reports are found working on the features and functions of the human telomere G-triplex (ht-G3) though the telomere G-quadruplex has been intensely studied and widely implemented to develop various biosensors. We herein report that ht-G3 lights up Thioflavin T (ThT) and establish a sensitive biosensing platform for RNA detection by introducing a target recycling strategy. An optimal condition was selected out for ht-G3 to promote ThT to generate a strong fluorescence.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!