GIANT HAIRPINS FORMED BY CUG REPEATS IN MYOTONIC-DYSTROPHY MESSENGER-RNAS MIGHT STERICALLY BLOCK RNA EXPORT THROUGH NUCLEAR-PORES

Energy minimization calculations were used to generate secondary struc tures of partial and full-length myotonic dystrophy messenger RNAs (DM PK mRNAs) carrying variable numbers of CUG triplet repeats (n = 0 to 5 00). The results suggest that (1) unitary hairpins are the most stable structures formed; (2) long-axis distances of unfolded hairpins are d irectly proportional to CUG repeat numbers; and (3) hairpins composed of CUG repeats might form interstem clusters that are stabilized by hy drogen or ionic bonds. A model is proposed whereby DMPK mRNAs are ster ically impeded from transport through nuclear pores, by giant hairpins or hairpin clusters formed by CUG repeats above a limit size (n great er than or equal to 44). (C) 1998 Academic Press.