Facile FMR1 mRNA structure regulation by interruptions in CGG repeats

Nucleic Acids Res. 2005 Jan 19;33(2):451-63. doi: 10.1093/nar/gki186. Print 2005.

Abstract

RNA metabolism is a major contributor to the pathogenesis of clinical disorders associated with premutation size alleles of the fragile X mental retardation (FMR1) gene. Herein, we determined the structural properties of numerous FMR1 transcripts harboring different numbers of both CGG repeats and AGG interruptions. The stability of hairpins formed by uninterrupted repeat-containing transcripts increased with the lengthening of the repeat tract. Even a single AGG interruption in the repeated sequence dramatically changed the folding of the 5'UTR fragments, typically resulting in branched hairpin structures. Transcripts containing different lengths of CGG repeats, but sharing a common AGG pattern, adopted similar types of secondary structures. We postulate that interruption-dependent structure variants of the FMR1 mRNA contribute to the phenotype diversity, observed in premutation carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / chemistry
  • Base Sequence
  • Fragile X Mental Retardation Protein
  • Humans
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nucleic Acid Conformation
  • RNA, Messenger / chemistry*
  • RNA-Binding Proteins / genetics*
  • Repetitive Sequences, Nucleic Acid
  • Trinucleotide Repeat Expansion

Substances

  • 5' Untranslated Regions
  • FMR1 protein, human
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Fragile X Mental Retardation Protein