4E6B: Crystal Structure of statistically disordered 19mer duplex p(CGG)3C(CUG)3

Human genetic trinucleotide repeat expansion diseases (TREDs) are characterized by triplet repeat expansions, most frequently found as CNG-tracts in genome. At RNA level, such expansions suggestively result in formation of double-helical hairpins that become a potential source for small RNAs involved in RNA interference (RNAi). Here, we present three crystal structures of RNA fragments composed of triplet repeats CUG and CGG/CUG, as well as two crystal structures of same triplets in a protein-bound state. We show that both 20mer pG(CUG)(6)C and 19mer pGG(CGG)(3)(CUG)(2)CC form A-RNA duplexes, in which U.U or G.U mismatches are flanked/stabilized by two consecutive Watson-Crick G.C base pairs resulting in high-stacking GpC steps in every third position of the duplex. Despite interruption of this regularity in another 19mer, p(CGG)(3)C(CUG)(3), the oligonucleotide still forms regular double-helical structure, characterized, however, by 12 bp (rather than 11 bp) per turn. Analysis of newly determined molecular structures reveals the dynamic aspects of U.U and G.U mismatching within CNG-repetitive A-RNA and in a protein-bound state, as well as identifies an additional mode of U.U pairing essential for its dynamics and sheds the light on possible role of regularity of trinucleotide repeats for double-helical RNA structure. Findings are important for understanding the structural behavior of CNG-repetitive RNA double helices implicated in TREDs.
PDB ID: 4E6BDownload
MMDB ID: 101218
PDB Deposition Date: 2012/3/15
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.47  Å
Biological Unit for 4E6B: tetrameric; determined by author
Molecular Components in 4E6B
Label Count Molecule
Nucleotides(2 molecules)
Molecule annotation
Molecule annotation
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