Structural diversity of triplet repeat RNAs

Krzysztof Sobczak, Gracjan Michlewski, Mateusz de Mezer, Elzbieta Kierzek, Jacek Krol, Marta Olejniczak, Ryszard Kierzek, Wlodzimierz J Krzyzosiak

Research output: Contribution to journalArticlepeer-review

Abstract

Tandem repeats of various trinucleotide motifs are present in the human transcriptome, but the functions of these regular sequences, which likely depend on the structures they form, are still poorly understood. To gain new insight into the structural and functional properties of triplet repeats in RNA, we have performed a biochemical structural analysis of the complete set of triplet repeat transcripts, each composed of a single sequence repeated 17 times. We show that these transcripts fall into four structural classes. The repeated CAA, UUG, AAG, CUU, CCU, CCA, and UAA motifs did not form any higher order structure under any analyzed conditions. The CAU, CUA, UUA, AUG, and UAG repeats are ordered according to their increasing tendency to form semistable hairpins. The repeated CGA, CGU, and all CNG motifs form fairly stable hairpins, whereas AGG and UGG repeats fold into stable G-quadruplexes. The triplet repeats that formed the most stable structures were characterized further by biophysical methods. UV-monitored structure melting revealed that CGG and CCG repeats form, respectively, the most and least stable hairpins of all CNG repeats. Circular dichroism spectra showed that the AGG and UGG repeat quadruplexes are formed by parallel RNA strands. Furthermore, we demonstrated that the different susceptibility of various triplet repeat transcripts to serum nucleases can be explained by the sequence and structural features of the tested RNAs. The results of this study provide a comprehensive structural foundation for the functional analysis of triplet repeats in transcripts.

Original languageEnglish
Pages (from-to)12755-12764
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number17
Early online date16 Feb 2010
DOIs
Publication statusPublished - 23 Apr 2010

Keywords

  • Circular Dichroism
  • Humans
  • Nucleic Acid Conformation
  • RNA
  • Ribonucleases
  • Transcription, Genetic
  • Trinucleotide Repeats
  • RNA/Metabolism
  • Gene Expression
  • RNA Folding
  • RNA-Protein Interaction
  • RNA Structure
  • G-quadruplex
  • G-tetraplex
  • RNS Structure Probing
  • Triplet Repeat Hairpin

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