Figure 1:

The CUG^exp / CCUG^exp toxic RNAs that cause myotonic dystrophy type 1 and 2 (DM1 and DM2), respectively, have been shown to form “slippery hairpins” in vitro that capture and sequester muscleblind-like (MBNL) proteins. A) The expanded CTG repeat in the DMPK 3’ UTR (colored light blue, coding sequence in grey) is transcribed into CUG^exp RNAs that consist of consecutive 5’-UGCU-3’ MBNL RNA binding motifs. MBNL proteins bind to and are sequestered by these RNAs in ribonuclear aggregates known as foci. B) Structural studies have revealed that the CUG^exp / CCUG^exp RNAs form “slippery hairpins” in vitro in which the CUG repeats dynamically shift and realign. These experimental observations suggest that these RNAs likely fold into metastable, dynamic secondary structures in vivo, although an outstanding question in the field is what structure(s) the CUG / CCUG repeats adopt in vivo. A single repeat unit is highlighted in red in each model RNA structure.