Abstract
Fragile X syndrome, the most common cause of inherited mental retardation, is caused by the absence of FMRP (Fragile X Mental Retardation Protein). FMRP is an RNA binding protein reported to be involved in translational control, notably at postsynaptic sites of protein synthesis as a part of a multiprotein/mRNA complex. One of the FMRP interactors, NUFIP1, is an RNA binding protein with an expression profile matching that of FMRP. We now show that in the nucleus NUFIP1 is localized in the nuclear matrix in RNA-containing structures lying in the proximity of, but not overlapping with, sites of nascent RNA. NUFIP1 is also present in the cytoplasm, where it is associated with ribosomes, similarly to FMRP. In neurons NUFIP1 can be detected in functional synaptoneurosomes, colocalizing with ribosomes. Consistent with its subcellular localization in both nucleus and cytoplasm, we show that NUFIP1 contains a functional CRM1-dependent nuclear export signal and is able to shuttle between these two cellular compartments. These findings suggest the involvement of NUFIP1 in the export and localization of mRNA and, in association with FMRP, in the regulation of local protein synthesis near synapses.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Active Transport, Cell Nucleus / genetics
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Animals
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Animals, Newborn
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Brain / metabolism
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Brain / ultrastructure
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Cell Compartmentation / genetics
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Cell Nucleus / metabolism*
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Cell Nucleus / ultrastructure
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Exportin 1 Protein
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Fragile X Mental Retardation Protein
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Fragile X Syndrome / genetics
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Fragile X Syndrome / metabolism*
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HeLa Cells
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Humans
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Karyopherins / genetics
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Karyopherins / metabolism
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Male
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Mice
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Microscopy, Electron
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Nerve Tissue Proteins / metabolism
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Nuclear Matrix / genetics
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Nuclear Matrix / metabolism
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Nuclear Matrix / ultrastructure
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Organelles / metabolism*
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Presynaptic Terminals / metabolism
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Presynaptic Terminals / ultrastructure
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Protein Biosynthesis / genetics
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RNA / biosynthesis
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RNA / genetics
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Rats
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Receptors, Cytoplasmic and Nuclear*
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Ribosomes / genetics
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Ribosomes / metabolism
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Ribosomes / ultrastructure
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Signal Transduction / genetics
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Synaptosomes
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Testis / metabolism
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Testis / ultrastructure
Substances
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FMR1 protein, human
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Fmr1 protein, mouse
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Fmr1 protein, rat
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Karyopherins
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NUFIP1 protein, human
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Nerve Tissue Proteins
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Nuclear Proteins
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RNA-Binding Proteins
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Receptors, Cytoplasmic and Nuclear
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Fragile X Mental Retardation Protein
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RNA