Year: 2026
Type: preprint
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.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1129260274, Functional Roles of Nascent RNA Structure in Regulating and Coordinating Gene Expression, Transitions: Evolving our Understanding of Dynamic RNA Folding and Function, NSF-Simons National Institute for Theory and Mathematics in Biology, Recruitment of First-Time, Tenure-Track Faculty Members, G9000188344, RNA Structure Modeling Using Physics and Sequence Comparison
OpenAlex ID: W7126208180