title: Zfrp8 forms a complex with fragile-X mental retardation protein and regulates its localization and function.
abstract: Fragile-X syndrome is the most commonly inherited cause of autism and mental disabilities. The Fmr1 (Fragile-X Mental Retardation 1) gene is essential in humans and Drosophila for the maintenance of neural stem cells, and Fmr1 loss results in neurological and reproductive developmental defects in humans and flies. FMRP (Fragile-X Mental Retardation Protein) is a nucleo-cytoplasmic shuttling protein, involved in mRNA silencing and translational repression. Both Zfrp8 and Fmr1 have essential functions in the Drosophila ovary. In this study, we identified FMRP, Nufip (Nuclear Fragile-X Mental Retardation Protein-interacting Protein) and Tral (Trailer Hitch) as components of a Zfrp8 protein complex. We show that Zfrp8 is required in the nucleus, and controls localization of FMRP in the cytoplasm. In addition, we demonstrate that Zfrp8 genetically interacts with Fmr1 and tral in an antagonistic manner. Zfrp8 and FMRP both control heterochromatin packaging, also in opposite ways. We propose that Zfrp8 functions as a chaperone, controlling protein complexes involved in RNA processing in the nucleus.
authors.affiliation: Rutgers University, Department of Molecular Biology, Cancer Institute of New Jersey, Waksman Institute, 190 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: William
authors.initials: W
authors.lastname: Tan
authors.affiliation: Rutgers University, Department of Molecular Biology, Cancer Institute of New Jersey, Waksman Institute, 190 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Schauder
authors.affiliation: Rutgers University, Department of Molecular Biology, Cancer Institute of New Jersey, Waksman Institute, 190 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Naryshkina
authors.affiliation: Rutgers University, Department of Molecular Biology, Cancer Institute of New Jersey, Waksman Institute, 190 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Minakhina
authors.affiliation: Rutgers University, Department of Molecular Biology, Cancer Institute of New Jersey, Waksman Institute, 190 Frelinghuysen Road, Piscataway, NJ 08854, USA. Electronic address: steward@waksman.rutgers.edu.
authors.forename: Ruth
authors.initials: R
authors.lastname: Steward
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007247:Infertility, Female / Q000235:genetics; D008297:Male; D009866:Oogenesis; D010053:Ovary / Q000002:abnormalities
chemical_list: D051017:Apoptosis Regulatory Proteins; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; C467328:FMR1 protein, Drosophila; C522153:Zfrp8 protein, Drosophila
keywords: FMRP; Trailer Hitch; Translational repression; Zfrp8