A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein.
Silenced expression of the FMR1 gene is responsible for the fragile X syndrome. The FMR1 gene codes for an RNA binding protein (FMRP), which can shuttle between the nucleus and the cytoplasm and is found associated to polysomes in the cytoplasm. By two-hybrid assay in yeast, we identified a novel protein interacting with FMRP: nuclear FMRP interacting protein (NUFIP). NUFIP mRNA expression is strikingly similar to that of the FMR1 gene in neurones of cortex, hippocampus and cerebellum. At the subcellular level, NUFIP colocalizes with nuclear isoforms of FMRP in a dot-like pattern. NUFIP presents a C2H2 zinc finger motif and a nuclear localization signal, but has no homology to known proteins and shows RNA binding activity in vitro. NUFIP does not interact with the FMRP homologues encoded by the FXR1 and FXR2 genes. Thus, these results indicate a specific nuclear role for FMRP.
Bardoni
B
B
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, CU de Strasbourg, France. bardoni@igbmc.u-strasbg.fr
Schenck
A
A
Mandel
J L
JL
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D008607:Intellectual Disability / Q000235:genetics*; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics; D016335:Zinc Fingers
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse; C403092:NUFIP1 protein, human