Reveal the structural dynamics of RNA & DNA in real time

A study led by Bo Sun at ShanghaiTech University explored how human telomerase RNA (hTR) forms and maintains stable G-quadruplex structures. Using LUMICKS C-Trap, they monitored real-time folding and unfolding of single hTR molecules, revealing:

• Multiple distinct G-quadruplex conformations exist, identifiable only by single-molecule force spectroscopy.
• Local RNA sequences strongly modulate the unfolding and refolding kinetics of these critical telomeric structures.
• These novel insights into G4 structural dynamics offer novel therapeutic strategies for targeting telomere-related diseases, including cancers and aging.

Researchers Christian Kaiser and Sarah Woodson at Johns Hopkins University investigated how expanded CAG repeats in HTT RNA influence misfolding and aggregation. By applying real-time single-molecule force measurements with LUMICKS C-Trap, they discovered:

• Healthy (normal) HTT RNA unfolds cooperatively in a single well-defined step.
• Expanded repeats unfold stepwise (“stick-slip” pattern) at lower forces, indicating non-cooperative behavior.
• Frequent partially unfolded structures self-associate, directly linking RNA misfolding dynamics to Huntington disease progression

A study led by the Neva Caliskan Lab at the Helmholtz Institute for RNA-Based Infection Research investigated how ZAP-S protein modulates SARS-CoV-2 frameshifting through altering the pseudoknot structure. By directly tracking the real-time pseudoknot structural dynamics in the presence or absence of ZAP-S using LUMICKS C-Trap, they revealed:

• ZAP-S binding destabilizes the RNA pseudoknot structure, preventing its refolding and impairing frameshifting activity essential for viral protein production.
• Reduced frameshifting efficiency means fewer essential viral proteins are produced, weakening the virus’s ability to replicate.
• Ultimately, viral replication is significantly reduced, highlighting ZAP-S interaction with the pseudoknot as a novel, targetable antiviral mechanism with clear translational potential.

A breakthrough study led by Michael Schlierf at TU Dresden in collaboration with Didier Mazel at Institut Pasteur investigated this mystery using single-molecule techniques. By applying controlled forces to individual DNA-IntI1 integrase complexes with LUMICKS C-Trap, they revealed:

• Efficiently recombining DNA sites form mechanically stable complexes with the IntI1 protein that resist forces up to high forces.
• Poorly recombining DNA sites form weaker protein-DNA complexes that break apart at lower forces.
• The mechanical stability of these IntI1-DNA complexes directly correlates with recombination efficiency in living bacteria, revealing a physical basis for genetic adaptation and a potential target for combating antibiotic resistance.