title: 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.affiliation: Dipartimento di Biologia, Università di Roma, Tor Vergata, Via della Ricerca Scientifica, 00133 Roma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zalfa
authors.forename: Marcello
authors.initials: M
authors.lastname: Giorgi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Primerano
authors.forename: Annamaria
authors.initials: A
authors.lastname: Moro
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Penta
authors.forename: Surya
authors.initials: S
authors.lastname: Reis
authors.forename: Ben
authors.initials: B
authors.lastname: Oostra
authors.forename: Claudia
authors.initials: C
authors.lastname: Bagni
mesh_terms: D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism; D016153:Genes, Suppressor / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020733:RNA, Small Cytoplasmic / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C117734:BC1 RNA; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse