Alternative titles; symbols
HGNC Approved Gene Symbol: NUFIP1
Cytogenetic location: 13q14.12 Genomic coordinates (GRCh38) : 13:44,939,249-44,989,471 (from NCBI)
The FMR1 gene (309550) encodes an RNA-binding protein (FMRP) that can shuttle between the nucleus and the cytoplasm and is found associated with polysomes in the cytoplasm. Using a yeast 2-hybrid assay, Bardoni et al. (1999) identified a novel protein interacting with FMRP, and they designated the protein NUFIP (nuclear FMRP-interacting protein). NUFIP mRNA expression was found to be strikingly similar to that of the FMR1 gene in neurons of cortex, hippocampus, and cerebellum. At the subcellular level, NUFIP colocalized with nuclear isoforms of FMRP in a dot-like pattern. NUFIP contains a C2H2 zinc finger motif and a nuclear localization signal. In vitro, NUFIP showed RNA-binding activity.
Bardoni et al. (1999) confirmed the interaction of NUFIP and FMRP in vitro by GST pull-down experiments and in vivo by coimmunoprecipitation in mammalian cells. No interaction was found between NUFIP and the FMRP homologs encoded by the FXR1 (600819) and FXR2 (605339) genes.
Wyant et al. (2018) performed quantitative proteomic analyses of rapidly isolated lysosomes and found that nutrient levels and mTOR (601231) dynamically modulate the lysosomal proteome. Upon mTORC1 inhibition, NUFIP1 redistributes from the nucleus to autophagosomes and lysosomes. Upon these conditions, NUFIP1 interacts with ribosomes and delivers them to autophagosomes by directly binding to microtubule-associated proteins 1A/1B light chain 3B (LC3B; 609604). The starvation-induced degradation of ribosomes via autophagy (ribophagy) depends on the capacity of NUFIP1 to bind LC3B and promotes cell survival. Wyant et al. (2018) propose that NUFIP1 is a receptor for the selective autophagy of ribosomes.
By somatic cell hybrid analysis and fluorescence in situ hybridization, Bardoni et al. (2000) mapped the NUFIP1 gene to chromosome 13q14 and an NUFIP1 pseudogene to chromosome 6q12.
Bardoni, B., Giglio, S., Schenck, A., Rocchi, M., Mandel, J. L. Assignment of NUFIP1 (nuclear FMRP interacting protein 1) gene to chromosome 13q14 and assignment of a pseudogene to chromosome 6q12. Cytogenet. Cell Genet. 89: 11-13, 2000. [PubMed: 10894927] [Full Text: https://doi.org/10.1159/000015580]
Bardoni, B., Schenck, A., Mandel, J. L. A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein. Hum. Molec. Genet. 8: 2557-2566, 1999. [PubMed: 10556305] [Full Text: https://doi.org/10.1093/hmg/8.13.2557]
Wyant, G. A., Abu-Remaileh, M., Frenkel, E. M., Laqtom, N. N., Dharamdasani, V., Lewis, C. A., Chan, S. H., Heinze, I., Ori, A., Sabatini, D. M. NUFIP1 is a ribosome receptor for starvation-induced ribophagy. Science 360: 751-758, 2018. [PubMed: 29700228] [Full Text: https://doi.org/10.1126/science.aar2663]