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 structures of partial and full-length myotonic dystrophy messenger RNAs (DMPK mRNAs) carrying variable numbers of CUG triplet repeats (n = 0 to 500). The results suggest that (1) unitary hairpins are the most stable structures formed; (2) long-axis distances of unfolded hairpins are directly proportional to CUG repeat numbers; and (3) hairpins composed of CUG repeats might form interstem clusters that are stabilized by hydrogen or ionic bonds. A model is proposed whereby DMPK mRNAs are sterically impeded from transport through nuclear pores, by giant hairpins or hairpin clusters formed by CUG repeats above a limit size (n > or = 44).
Department of Pharmacology, University of California at San Diego, La Jolla 92093-0636, USA.
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Koch
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Leffert
D003198:Computer Simulation; D006801:Humans; D008957:Models, Genetic; D009223:Myotonic Dystrophy / Q000235:genetics*; D065636:Myotonin-Protein Kinase; D009685:Nuclear Envelope / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D018911:Trinucleotide Repeats
C585517:DMPK protein, human; D012333:RNA, Messenger; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases