Human Molecular Genetics, 2000, Vol. 9, No. 10 1487-1493
© 2000 Oxford University Press
The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins
Department of Clinical Genetics and Centre for Biomedical Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands and 1Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, TX 77030, USA
Fragile X syndrome is caused by the absence of the fragile X mental-retardation protein (FMRP). FMRP and the fragile X-related proteins 1 and 2 (FXR1P and FXR2P) form a gene family with functional similarities, such as RNA binding, polyribosomal association and nucleocytoplasmic shuttling. In a previous study, we found that FMRP and FXR1P shuttle between cytoplasm and nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. The nuclear and nucleolar-targeting properties of these proteins were investigated further. Here, we show that FXR2P contains in its C-terminal part, a stretch of basic amino acids ‘RPQRRNRSRRRRFR’ that resemble the nucleolar-targeting signal (NoS) of the viral protein Rev. This particular sequence is also present within exon 15 of the FXR1 gene. This exon undergoes alternative splicing and is therefore only present in some of the FXR1P isoforms. We investigated the intracellular distribution of various FXR1P isoforms with (iso-e and iso-f) and without (iso-d) the potential NoS in transfected COS cells treated with the nuclear export inhibitor leptomycin-B. Both iso-e and iso-f showed a nucleolar localization, as observed for FXR2P; iso-d was detected in the nucleoplasm outside the nucleoli. Further, when a labelled 16-residue synthetic peptide corresponding to the NoS of FXR1P was added to human fibroblast cultures a clear nucleolar signal was observed. Based on these data we argue that the intranuclear distribution of FXR2P and FXR1P isoforms is very likely to be mediated by a similar NoS localized in their C-terminal region. This domain is absent in some FXR1P isoforms as well as in all FMRP isoforms, suggesting functional differences for this family of proteins, possibly related to RNA metabolism in different tissues.
+ To whom correspondence should be addressed. Tel: +31 104087355; Fax: +31 104089489; Email: hoogeveen@ikg.fgg.eur.nl
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Ju, C. A. Valencia, H. Pang, Y. Ke, W. Gao, B. Dong, and R. Liu Proteome-wide identification of family member-specific natural substrate repertoire of caspases PNAS, September 4, 2007; 104(36): 14294 - 14299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Davidovic, E. Bechara, M. Gravel, X. H. Jaglin, S. Tremblay, A. Sik, B. Bardoni, and E. W. Khandjian The nuclear MicroSpherule protein 58 is a novel RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal mRNPs from neurons Hum. Mol. Genet., May 1, 2006; 15(9): 1525 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. M. Bontekoe, K. L. McIlwain, I. M. Nieuwenhuizen, L. A. Yuva-Paylor, A. Nellis, R. Willemsen, Z. Fang, L. Kirkpatrick, C. E. Bakker, R. McAninch, et al. Knockout mouse model for Fxr2: a model for mental retardation Hum. Mol. Genet., March 1, 2002; 11(5): 487 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-E. Huot, R. Mazroui, P. Leclerc, and E. W. Khandjian Developmental expression of the fragile X-related 1 proteins in mouse testis: association with microtubule elements Hum. Mol. Genet., November 1, 2001; 10(24): 2803 - 2811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Laggerbauer, D. Ostareck, E.-M. Keidel, A. Ostareck-Lederer, and U. Fischer Evidence that fragile X mental retardation protein is a negative regulator of translation Hum. Mol. Genet., February 1, 2001; 10(4): 329 - 338. [Abstract] [Full Text] [PDF]
|
|