The fragile X mental retardation protein binds and regulates a novel class of mRNAs containing U rich target sequences

Neuroscience. 2003;120(4):1005-17. doi: 10.1016/s0306-4522(03)00406-8.

Abstract

Fragile X syndrome is a common form of inherited mental retardation caused by the absence of the fragile X mental retardation protein (FMRP). It has been hypothesized that FMRP is involved in the processing and/or translation of mRNAs. Human and mouse target-mRNAs, containing purine quartets, have previously been identified. By using cDNA-SELEX (systematic evolution of ligands by exponential enrichment), we identified another class of human target-mRNAs which contain U rich sequences. This technique, in contrast to oligonucleotide-based SELEX, allows the identification of FMRP targets directly from mRNA pools. Many of the proteins encoded by the identified FMRP targets have been implicated in neuroplasticity. Steady state levels of target-mRNAs were unchanged in the brain of fragile X mice. However, levels of two target-encoded proteins, an L-type calcium channel subunit and MAP1B, were downregulated in specific brain regions suggesting a defect in the expression of target-encoded proteins in fragile X syndrome.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Bacteria
  • Base Sequence / genetics
  • Blotting, Western
  • Brain / anatomy & histology
  • Brain / metabolism
  • Cell Line
  • Clathrin / genetics
  • Clathrin / metabolism
  • Dose-Response Relationship, Drug
  • Electrophoretic Mobility Shift Assay
  • Embryo, Mammalian
  • Embryo, Nonmammalian
  • Fetus
  • Fragile X Mental Retardation Protein
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Guanine Nucleotide Dissociation Inhibitors / metabolism
  • Humans
  • In Vitro Techniques
  • Insecta
  • Kidney
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Mucins / genetics
  • Mucins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oligopeptides
  • Peptides / metabolism
  • Phosphopyruvate Hydratase / genetics
  • Phosphopyruvate Hydratase / metabolism
  • Protein Binding
  • RNA, Messenger / metabolism
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / metabolism
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sequence Homology, Amino Acid
  • Uridine / genetics
  • Uridine / metabolism*
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Clathrin
  • FMR1 protein, human
  • Fmr1 protein, mouse
  • Guanine Nucleotide Dissociation Inhibitors
  • Microtubule-Associated Proteins
  • Mucins
  • Nerve Tissue Proteins
  • Oligopeptides
  • Peptides
  • RNA, Messenger
  • RNA-Binding Protein FUS
  • RNA-Binding Proteins
  • microtubule-associated protein 1B
  • Fragile X Mental Retardation Protein
  • FLAG peptide
  • Adenosine Triphosphatases
  • rhoA GTP-Binding Protein
  • Phosphopyruvate Hydratase
  • Uridine