A Slow Exchange Model of Non-rigid Rotational Motion in RNA for combined Solid-state and Solution NMR studies

摘要

Functional RNA molecules are conformationally dynamic and sample a multitude of dynamic modes over a wide range of frequencies. Thus, a comprehensive description of RNA dynamics requires the inclusion of a broad range of motions across multiple dynamic rates which must be derived from multiple spectroscopies. Here we describe a slow conformational exchange theoretical approach to combining the description of local motions in RNA that occur in the ns-μs window and are detected by solid-state NMR with non-rigid rotational motion of the HIV-1 TAR RNA in solution as observed by solution NMR. This theoretical model unifies the experimental results generated by solution and solid-state NMR and provides a comprehensive view of the dynamics of HIV-1 TAR RNA, a well-known paradigm of an RNA where function requires extensive conformational rearrangements. This methodology provides a quantitative atomic level view of the amplitudes and rates of the local and collective displacements of the TAR RNA molecule, and provides directly motional parameters for the conformational capture hypothesis of this classical RNA-ligand interaction.