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Crystal Structure of statistically disordered 19mer duplex p(CGG)3C(CUG)3Crystal Structure of statistically disordered 19mer duplex p(CGG)3C(CUG)3
Structural highlights
Publication Abstract from PubMedHuman 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. Structural dynamics of double-helical RNAs composed of CUG/CUG- and CUG/CGG-repeats.,Tamjar J, Katorcha E, Popov A, Malinina L J Biomol Struct Dyn. 2012 Jun 25. PMID:22731704[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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