PMID- 10196376
OWN - NLM
STAT- MEDLINE
DCOM- 19990623
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 5
DP  - 1999 May
TI  - Different targets for the fragile X-related proteins revealed by their distinct
      nuclear localizations.
PG  - 863-9
AB  - 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.
FAU - Tamanini, F
AU  - Tamanini F
AD  - Department of Clinical Genetics and Center for Biomedical Genetics, Erasmus
      University, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
FAU - Bontekoe, C
AU  - Bontekoe C
FAU - Bakker, C E
AU  - Bakker CE
FAU - van Unen, L
AU  - van Unen L
FAU - Anar, B
AU  - Anar B
FAU - Willemsen, R
AU  - Willemsen R
FAU - Yoshida, M
AU  - Yoshida M
FAU - Galjaard, H
AU  - Galjaard H
FAU - Oostra, B A
AU  - Oostra BA
FAU - Hoogeveen, A T
AU  - Hoogeveen AT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Adhesins, Bacterial)
RN  - 0 (Carrier Proteins)
RN  - 0 (FMR1 protein, human)
RN  - 0 (FXR1 protein, human)
RN  - 0 (FXR2 protein, human)
RN  - 0 (Karyopherins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Ribosomal)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (exportin 1 protein)
RN  - 04Y7590D77 (Isoleucine)
RN  - 139135-51-6 (Fragile X Mental Retardation Protein)
RN  - 7006-34-0 (Asparagine)
SB  - IM
MH  - Adhesins, Bacterial/pharmacology
MH  - Animals
MH  - Asparagine
MH  - COS Cells/drug effects/metabolism
MH  - Carrier Proteins/metabolism
MH  - Cell Nucleus/drug effects/genetics/*metabolism
MH  - Cytoplasm
MH  - Fragile X Mental Retardation Protein
MH  - Fragile X Syndrome/*genetics/metabolism
MH  - Humans
MH  - Isoleucine
MH  - *Karyopherins
MH  - Mutation
MH  - Nerve Tissue Proteins/drug effects/genetics/*metabolism
MH  - RNA, Messenger/genetics
MH  - RNA, Ribosomal/genetics
MH  - RNA-Binding Proteins/drug effects/genetics/*metabolism
MH  - *Receptors, Cytoplasmic and Nuclear
MH  - Transcription, Genetic
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - ddc094 [pii]
AID - 10.1093/hmg/8.5.863 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 May;8(5):863-9. doi: 10.1093/hmg/8.5.863.