Structure of an RNA helix with pyrimidine mismatches and cross-strand stacking

The structure of a 22-base-pair RNA helix with mismatched pyrimidine base pairs is reported. The helix contains two symmetry-related CUG sequences: a triplet-repeat motif implicated in myotonic dystrophy type 1. The CUG repeat contains a U–U mismatch sandwiched between Watson–Crick pairs. Additionally, the center of the helix contains a dimerized UUCG motif with tandem pyrimidine (U–C/C–U) mismatches flanked by U–G wobble pairs. This region of the structure is significantly different from previously observed structures that share the same sequence and neighboring base pairs. The tandem pyrimidine mismatches are unusual and display sheared, cross-strand stacking geometries that locally constrict the helical width, a type of stacking previously associated with purines in internal loops. Thus, pyrimidine-rich regions of RNA have a high degree of structural diversity.