The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses.

Abstract

The Fragile X syndrome, which results from the absence of functional FMRP protein, is the most common heritable form of mental retardation. Here, we show that FMRP acts as a translational repressor of specific mRNAs at synapses. Interestingly, FMRP associates not only with these target mRNAs, but also with the dendritic, non-translatable RNA BC1. Blocking of BC1 inhibits the interaction of FMRP with its target mRNAs. Furthermore, BC1 binds directly to FMRP and can also associate, in the absence of any protein, with the mRNAs regulated by FMRP. This suggests a mechanism where BC1 could determine the specificity of FMRP function by linking the regulated mRNAs and FMRP. Thus, when FMRP is not present, loss of translational repression of specific mRNAs at synapses could result in synaptic dysfunction phenotype of Fragile X patients.

• Authors: Francesca Zalfa, Marcello Giorgi, Beatrice Primerano, Annamaria Moro, Alessandra Di Penta, Surya Reis, Ben Oostra, Claudia Bagni
• Journal: Cell (Cell) Vol. 112 Issue 3 Pg. 317-27 (Feb 07 2003) ISSN: 0092-8674 [Print] United States
• PMID: 12581522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• BC1 RNA
• FMR1 protein, human
• Fmr1 protein, mouse
• Macromolecular Substances
• Nerve Tissue Proteins
• RNA, Messenger
• RNA, Small Cytoplasmic
• RNA-Binding Proteins
• Ribonucleoproteins
• Fragile X Mental Retardation Protein

Topics

• Animals
• Base Sequence (genetics)
• Brain (growth & development, metabolism)
• Dendrites (metabolism)
• Fragile X Mental Retardation Protein
• Fragile X Syndrome (genetics, metabolism)
• Genes, Suppressor (physiology)
• Humans
• Macromolecular Substances
• Mice
• Mice, Knockout
• Molecular Sequence Data
• Molecular Structure
• Nerve Tissue Proteins (deficiency, genetics)
• Protein Binding (genetics)
• Protein Biosynthesis (genetics)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Cytoplasmic (genetics, metabolism)
• RNA-Binding Proteins
• Ribonucleoproteins (genetics, metabolism)
• Synapses (genetics, metabolism)
• Synaptic Transmission (genetics)
• Tumor Cells, Cultured