Resolving the Motional Modes That Code for RNA Adaptation

• Published in: Science (American Association for the Advancement of Science) Vol. 311; no. 5761; pp. 653 - 656
• Main Authors: Zhang, Qi, Sun, Xiaoyan, Watt, Eric D, Al-Hashimi, Hashim M
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 03-02-2006; The American Association for the Advancement of Science
• Subjects: Adaptation; Amplitude; Arginine - analogs & derivatives; Arginine - metabolism; Base Pairing; Biological and medical sciences; Conformational dynamics in molecular biology; Conformity; Fundamental and applied biological sciences. Psychology; Guanine - chemistry; HIV; HIV 1; HIV Long Terminal Repeat; HIV-1 - genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Hydrodynamics; Kinetics; Molecular biophysics; NMR; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Nucleic Acid Conformation; Ribonucleic acid; RNA; RNA, Double-Stranded - chemistry; RNA, Double-Stranded - genetics; RNA, Viral - chemistry; RNA, Viral - metabolism; Rotation; Spectrum analysis; Sugars; Time constants; Uridine - chemistry; Nuclear magnetic resonance; RNA; Conformational dynamics; Adaptation; Conformation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1119488

Using a domain elongation strategy, we decoupled internal motions in RNA from overall rotational diffusion. This allowed us to site-specifically resolve a manifold of motional modes in two regulatory RNAs from HIV-1 with the use of nuclear magnetic resonance spin relaxation methods. Base and sugar librations vary on a picosecond time scale and occur within helical domains that move collectively at diffusion-limited nanosecond time scales. Pivot points are short, functionally important, and highly mobile internal loops. These spontaneous changes in RNA conformation correlate quantitatively with those that follow adaptive recognition of diverse targets. Thus, ligands may stabilize existing RNA conformations rather than inducing new ones.