Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome.

Published

Journal Article

Fragile X syndrome results from the absence of the RNA binding FMR protein. Here, mRNA was coimmunoprecipitated with the FMRP ribonucleoprotein complex and used to interrogate microarrays. We identified 432 associated mRNAs from mouse brain. Quantitative RT-PCR confirmed some to be >60-fold enriched in the immunoprecipitant. In parallel studies, mRNAs from polyribosomes of fragile X cells were used to probe microarrays. Despite equivalent cytoplasmic abundance, 251 mRNAs had an abnormal polyribosome profile in the absence of FMRP. Although this represents <2% of the total messages, 50% of the coimmunoprecipitated mRNAs with expressed human orthologs were found in this group. Nearly 70% of those transcripts found in both studies contain a G quartet structure, demonstrated as an in vitro FMRP target. We conclude that translational dysregulation of mRNAs normally associated with FMRP may be the proximal cause of fragile X syndrome, and we identify candidate genes relevant to this phenotype.

Full Text

Duke Authors

Cited Authors

  • Brown, V; Jin, P; Ceman, S; Darnell, JC; O'Donnell, WT; Tenenbaum, SA; Jin, X; Feng, Y; Wilkinson, KD; Keene, JD; Darnell, RB; Warren, ST

Published Date

  • November 16, 2001

Published In

Volume / Issue

  • 107 / 4

Start / End Page

  • 477 - 487

PubMed ID

  • 11719188

Pubmed Central ID

  • 11719188

International Standard Serial Number (ISSN)

  • 0092-8674

Language

  • eng

Conference Location

  • United States