Elucidating OASL-RNA Interactions: Structural and energetic insights into vault RNAs binding

Oligoadenylate synthetase-like (OASL) proteins play an essential role in the innate immune response by detecting RNA molecules and modulating antiviral signalling pathways. This study investigated the structural and functional dynamics of OASL in its interaction with endogenous vault RNAs (vtRNAs) through computational analyses, including molecular docking and molecular dynamics simulations. Predicted 3D structures of vtRNAs revealed key interactions within the positively charged RNA-binding groove of OASL, involving residues such as Arg45, Lys63, and Arg196. Among the vtRNAs analysed, vtRNA 1-1 exhibited the highest binding affinity and stability, inducing conformational changes in OASL consistent with canonical activation mechanisms. In contrast, vtRNA 1-2 and 1-3 demonstrated moderate interactions, while vtRNA 2-1 had minimal impact on OASL conformation. Our results underscore the critical role of guanine- and cytosine-enriched regions in mediating binding stability and specificity, as corroborated by MM/GBSA calculations. The study highlights the molecular determinants of OASL-vtRNA interactions, offering structural insights into the mechanisms of nucleic acid recognition.