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.

Zalfa F., G.M. (2003). The Fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses, 112(3), 317-327 [10.1016/S0092-8674(03)00079-5].

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

BAGNI, CLAUDIA
2003

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/13
English
Con Impact Factor ISI
fragile X mental retardation protein; messenger RNA; RNA; animal tissue; article; binding kinetics; controlled study; dendrite; human; human cell; mouse; nonhuman; priority journal; protein function; protein RNA binding; regulatory mechanism; synapse; translation regulation; Animals; Base Sequence; Brain; Dendrites; Fragile X Mental Retardation Protein; Fragile X Syndrome; Genes, Suppressor; Humans; Macromolecular Substances; Mice; Mice, Knockout; Molecular Sequence Data; Molecular Structure; Nerve Tissue Proteins; Protein Binding; Protein Biosynthesis; Ribonucleoproteins; RNA, Messenger; RNA, Small Cytoplasmic; RNA-Binding Proteins; Synapses; Synaptic Transmission; Tumor Cells, Cultured; Animalia
Zalfa F., G.M. (2003). The Fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses, 112(3), 317-327 [10.1016/S0092-8674(03)00079-5].
Zalfa, F; Giorgi, M; Primerano, B; Moro, A; Di Penta, A; Reis, S; Oostra, B; Bagni, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/51834
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