Probing the structural hierarchy and energy landscape of an RNA T-loop hairpin.
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.
Zhuang
Zhuoyun
Z
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106-9510, USA.
Jaeger
Luc
L
Shea
Joan-Emma
JE
D019614:Haloarcula marismortui / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics
D012313:RNA