Integrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution

• Published in: Nature communications Vol. 15; no. 1; p. 4367
• Main Authors: Ward, Shannon, Childs, Alex, Staley, Ceri, Waugh, Christopher, Watts, Julie A., Kotowska, Anna M., Bhosale, Rahul, Borkar, Aditi N.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 101/58; 45/90; 631/1647/296; 631/45/500; 631/535/1267; Atomic properties; Atomic structure; Biology; Chemical reactions; Computer applications; Humanities and Social Sciences; Integrated approach; Mass spectrometry; Mass Spectrometry - methods; Mass spectroscopy; Models, Molecular; Molecular Dynamics Simulation; Molecular interactions; multidisciplinary; Nucleic Acid Conformation; Ribonucleic acid; Ribonucleoproteins - chemistry; RNA; RNA - chemistry; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-48694-3

The 3D architecture of RNAs governs their molecular interactions, chemical reactions, and biological functions. However, a large number of RNAs and their protein complexes remain poorly understood due to the limitations of conventional structural biology techniques in deciphering their complex structures and dynamic interactions. To address this limitation, we have benchmarked an integrated approach that combines cryogenic OrbiSIMS, a state-of-the-art solid-state mass spectrometry technique, with computational methods for modelling RNA structures at atomic resolution with enhanced precision. Furthermore, using 7SK RNP as a test case, we have successfully determined the full 3D structure of a native RNA in its apo, native and disease-remodelled states, which offers insights into the structural interactions and plasticity of the 7SK complex within these states. Overall, our study establishes cryo-OrbiSIMS as a valuable tool in the field of RNA structural biology as it enables the study of challenging, native RNA systems. Conventional structural biology techniques are limited in deciphering complex RNA structures and dynamic interactions. Here the authors show an integrated approach that combines cryogenic OrbiSIMS (cryo-OrbiSIMS) with computational methods for modelling RNA structures at atomic resolution.