ArticlebioRxiv : the preprint server for biology2026
Ubiquitous low-energy RNA fluctuations and energetic coupling measured by chemical probing.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
5 authors.
Funding
Abstract
RNA function is governed by RNA folding, but strategies for measuring RNA folding thermodynamics are limited, and fundamental questions such as the energy of base pair opening remain debated. Here we introduce Probing-Resolved Inference of Molecular Energetics (PRIME) to extract nucleotide-resolution RNA structural energetics from scalable chemical probing experiments. Applying PRIME to diverse RNAs, we find that RNA base pairs and tertiary interactions dynamically open with free energies of 0.5-3 kcal/mol, revealing that RNA nucleotides ubiquitously sample open conformations at biologically accessible energies. PRIME further resolves energetic coupling across RNAs, providing an energetic understanding of RNA structural dynamics and long-range coordination in RNA folding. PRIME represents a widely accessible strategy for interrogating RNA thermodynamics, enabling mechanistic understanding and engineering of RNA biology.
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Registered trials
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