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

L. Chen, S. W. Yun, J. Seto, W. Liu, M. Toth

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

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.

Original languageEnglish
Pages (from-to)1005-1017
Number of pages13
JournalNeuroscience
Volume120
Issue number4
DOIs
StatePublished - 15 Sep 2003
Externally publishedYes

Keywords

  • FMRP
  • L-type calcium channel
  • U rich mRNA
  • cDNA-SELEX
  • mRNP

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