4E5C

Crystal Structure of 19mer double-helical RNA containing CUG/CGG-repeats

4E5C の概要

• エントリーDOI: 10.2210/pdb4e5c/pdb
• 関連するPDBエントリー: 4E48
• 分子名称: 5'-R(P*GP*GP*CP*GP*GP*CP*GP*GP*CP*GP*GP*CP*UP*GP*CP*UP*GP*CP*C)-3' (2 entities in total)
• 機能のキーワード: sirna, trinucleotide repeat expansion, rna
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12311.41

構造登録者

Malinina, L.,Popov, A.,Tamjar, J. (登録日: 2012-03-14, 公開日: 2012-07-11, 最終更新日: 2024-02-28)

主引用文献

Tamjar, J.,Katorcha, E.,Popov, A.,Malinina, L.
Structural dynamics of double-helical RNAs composed of CUG/CUG- and CUG/CGG-repeats.
J.Biomol.Struct.Dyn., 30:505-523, 2012

PubMed Abstract: 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.

PubMed: 22731704
DOI: 10.1080/07391102.2012.687517

実験手法

X-RAY DIFFRACTION (1.7 Å)