Analysis of natural structures and chemical mapping data reveals local stability compensation in RNA.

ABSTRACT: RNA molecules adopt complex structures that perform essential biological functions across all forms of life, making them promising candidates for therapeutic applications. However, our ability to design new RNA structures remains limited by an incomplete understanding of their folding principles. While global metrics such as the minimum free energy are widely used, they are at odds with naturally occurring structures and incompatible with established design rules. Here, we introduce local stability compensation (LSC), a principle that RNA folding is governed by the local balance between destabilizing loops and their stabilizing adjacent stems, challenging the focus on global energetic optimization. Analysis of over 100,000 RNA structures revealed that LSC signatures are particularly pronou

SUBMITTER: Cornwell-Arquitt RL 

PROVIDER: S-EPMC11661157 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature