Mechanisms and Evolutionary Perspectives of RNA Chaperones in RNA Folding and Function

RNA molecules face significant challenges in achieving their correct functional structures due to intrinsic folding problems, including kinetic trapping in incorrect conformations and thermodynamic instability of tertiary structures. The RNA chaperone hypothesis proposes that RNA-binding proteins, or RNA chaperones, play a crucial role in facilitating proper RNA folding by mitigating these difficulties. RNA chaperones resolve misfolding by preventing alternative conformations and stabilizing correct tertiary structures, thus enhancing RNA functionality. This hypothesis is supported by evidence demonstrating that nonspecific RNA-binding proteins enhance RNA folding kinetics by resolving misfolded complexes.RNA-dependent ATPases are implicated in the spatial and temporal regulation of RNA folding. The evolutionary transition from an RNA-dominated world to an RNA-protein world is thought to have involved the emergence of nonspecific RNA-binding peptides that initially functioned as general chaperones before evolving into more specialized RNA-binding proteins. The role of RNA chaperones extends to the regulation of ribosomal RNA folding, where assembly factors prevent misfolding by delaying tertiary interactions.Mechanistic insights into RNA chaperone function reveal diverse strategies, including charge screening and specific binding interactions, which facilitate RNA conformational transitions. This review aims to provide a comprehensive overview of the mechanisms by which RNA chaperones influence RNA folding and to explore the evolutionary implications of these interactions.