Dehydration-Responsive Left-Handed G-Quadruplexes Expandthe Sequence Repertoire
- 1Inserm / Ecole Polytechnique
Abstract
G-quadruplexes (G4s) are widely studied noncanonical nucleic-acid structures that carry important biological functions. Typically, G4s form from G-rich sequences containing at least four tracts of more than two consecutive guanines, yet a plethora of unconventional G4-forming sequences have been identified, including sequences that fold into G4s only under specific conditions. These G4 states remain poorly resolved. Here we identify dehydration-responsive left-handed G4s (drLHG4s), a class of left-handed G4 (LHG4) structures accessible under dehydrating conditions. Using d(GT)n repeats, we show that left-handed folding depends on repeat length, salt condition and solvent conditions. Systematic mutational analysis reveals a broader but register-constrained sequence space, while high-resolution crystal structures of d-GTGGTGTGTGGTG, a sequence that folded robustly under dehydrating conditions, establish a bulged LHG4 architecture and reveal a distinctive hydration sphere. We further show that selected peptides and a cationic zinc phthalocyanine derivative, ZnTEGQPyrPc, containing four triethylene glycol methyl ether tails can induce LHG4 states. Together, our findings reveal a dehydration-responsive G4 landscape and expand the experimentally accessible sequence space of LHG4 folding.
Related
- Mosaic divergent repeat interruptions of motif length and sequence, mDRILS, of XDP-linked repeats affect formation of DNA/RNA triplexes & quadruplexes
- A Solution-Gated Graphene Transistor Sensor for the Detection and Quantification of Guanine Quadruplexes.
- G-Quadruplexes at the ‘Interface’ of Transcription and Alternative Splicing
- G-quadruplexes in the proximity 3′-UTR enhances alternative polyadenylation of Neogenin 1
- Dehydration triggers anomalous subdiffusion in biomimetic cell membranes
BibTeX
@misc{chen2026dehydrationresponsive,
title = {{Dehydration-Responsive Left-Handed G-Quadruplexes Expandthe Sequence Repertoire}},
author = {Y. Chen and A. Hendrickson and J. Gros and E. Xing and E. R. Windle and J. Wang and R. M. Edkins and S. J. Quinn and L. A. Yatsunyk and J.-L. Mergny},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756892},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756892v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Dehydration-Responsive Left-Handed G-Quadruplexes Expandthe Sequence Repertoire
AU - Y. Chen
AU - A. Hendrickson
AU - J. Gros
AU - E. Xing
AU - E. R. Windle
AU - J. Wang
AU - R. M. Edkins
AU - S. J. Quinn
AU - L. A. Yatsunyk
AU - J.-L. Mergny
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.756892
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.756892v1
AB - G-quadruplexes (G4s) are widely studied noncanonical nucleic-acid structures that carry important biological functions. Typically, G4s form from G-rich sequences containing at least four tracts of more than two consecutive guanines, yet a plethora of unconventional G4-forming sequences have been identified, including sequences that fold into G4s only under specific conditions. These G4 states remain poorly resolved. Here we identify dehydration-responsive left-handed G4s (drLHG4s), a class of left-handed G4 (LHG4) structures accessible under dehydrating conditions. Using d(GT)n repeats, we show that left-handed folding depends on repeat length, salt condition and solvent conditions. Systematic mutational analysis reveals a broader but register-constrained sequence space, while high-resolution crystal structures of d-GTGGTGTGTGGTG, a sequence that folded robustly under dehydrating conditions, establish a bulged LHG4 architecture and reveal a distinctive hydration sphere. We further show that selected peptides and a cationic zinc phthalocyanine derivative, ZnTEGQPyrPc, containing four triethylene glycol methyl ether tails can induce LHG4 states. Together, our findings reveal a dehydration-responsive G4 landscape and expand the experimentally accessible sequence space of LHG4 folding.
ER -