Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations

F Tamanini; C Bontekoe; C E Bakker; L van Unen; B Anar; R Willemsen; M Yoshida; H Galjaard; B A Oostra; A T Hoogeveen

doi:10.1093/hmg/8.5.863

Different targets for the fragile X-related proteins revealed by their distinct nuclear localizations

Hum Mol Genet. 1999 May;8(5):863-9. doi: 10.1093/hmg/8.5.863.

Authors

F Tamanini¹, C Bontekoe, C E Bakker, L van Unen, B Anar, R Willemsen, M Yoshida, H Galjaard, B A Oostra, A T Hoogeveen

Affiliation

¹ Department of Clinical Genetics and Center for Biomedical Genetics, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands.

PMID: 10196376
DOI: 10.1093/hmg/8.5.863

Abstract

Fragile X syndrome is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP and its structural homologues FXR1P and FXR2P form a family of RNA-binding proteins (FXR proteins). The three proteins associate with polyribosomes as cytoplasmic mRNP particles. Here we show that small amounts of FMRP, FXR1P and FXR2P shuttle between cytoplasm and nucleus. Mutant FMRP of a severely affected fragile X patient (FMRPI304N) does not associate with polyribosomes and shuttles more frequently than normal FMRP, indicating that the association with polyribosomes regulates the shuttling process. Using leptomycin B we demonstrate that transport of the FXR proteins out of the nucleus is mediated by the export receptor exportin1. Finally, inactivation of the nuclear export signal in two FXR proteins shows that FMRP shuttles between cytoplasm and nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. Therefore, molecular dissection of the shuttling routes used by the FXR proteins suggests that they transport different RNAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adhesins, Bacterial / pharmacology
Animals
Asparagine
COS Cells / drug effects
COS Cells / metabolism
Carrier Proteins / metabolism
Cell Nucleus / drug effects
Cell Nucleus / genetics
Cell Nucleus / metabolism*
Cytoplasm
Exportin 1 Protein
Fragile X Mental Retardation Protein
Fragile X Syndrome / genetics*
Fragile X Syndrome / metabolism
Humans
Isoleucine
Karyopherins*
Mutation
Nerve Tissue Proteins / drug effects
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
RNA, Messenger / genetics
RNA, Ribosomal / genetics
RNA-Binding Proteins / drug effects
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
Receptors, Cytoplasmic and Nuclear*
Transcription, Genetic

Substances

Adhesins, Bacterial
Carrier Proteins
FMR1 protein, human
FXR1 protein, human
FXR2 protein, human
Karyopherins
Nerve Tissue Proteins
RNA, Messenger
RNA, Ribosomal
RNA-Binding Proteins
Receptors, Cytoplasmic and Nuclear
Isoleucine
Fragile X Mental Retardation Protein
Asparagine