title: Probing the structural hierarchy and energy landscape of an RNA T-loop hairpin.
abstract: The T-loop motif is an important recurrent RNA structural building block consisting of a U-turn sub-motif and a UA trans Watson-Crick/Hoogsteen base pair. In the presence of a hairpin stem, the UA non-canonical base pair becomes part of the UA-handle motif. To probe the hierarchical organization and energy landscape of the T-loop, we performed replica exchange molecular dynamics (REMD) simulations of the T-loop in isolation and as part of a hairpin. Our simulations reveal that the isolated T-loop adopts coil conformers stabilized by base stacking. The T-loop hairpin shows a highly rugged energy landscape featuring multiple local minima with a transition state for folding consisting of partially zipped states. The U-turn displays a high conformational flexibility both when the T-loop is in isolation and as part of a hairpin. On the other hand, the stability of the UA non-canonical base pair is enhanced in the presence of the UA-handle. This motif is apparently a key component for stabilizing the T-loop, while the U-turn is mostly involved in long-range interaction. Our results suggest that the stability and folding of small RNA motifs are highly dependent on local context.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106-9510, USA.
authors.forename: Zhuoyun
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Luc
authors.initials: L
authors.lastname: Jaeger
authors.forename: Joan-Emma
authors.initials: JE
authors.lastname: Shea
mesh_terms: D019614:Haloarcula marismortui / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D012313:RNA