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Proc Natl Acad Sci U S A
1997 Dec 23;9426:14394-9. doi: 10.1073/pnas.94.26.14394.
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Inhibition of mRNA export in vertebrate cells by nuclear export signal conjugates.
Pasquinelli AE
,
Powers MA
,
Lund E
,
Forbes D
,
Dahlberg JE
.
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Leucine-rich nuclear export signals (NESs) are recognized by the NES receptor exportin 1 and are central to the export of multiple shuttling proteins and RNAs. The export of messenger RNA in vertebrates was, however, thought to occur by a different pathway, because inhibition by injection of a synthetic Rev NES conjugate could not be demonstrated. Here we find that peptide conjugates composed of the NES of either protein kinase A inhibitor protein (PKI) or the HIV-1 Rev protein, when coupled to human serum albumin, are potent inhibitors of mRNA and small nuclear RNA export. These results provide direct evidence that mRNA export in vertebrates depends on interactions between an NES and its cognate NES receptors. PKI NES conjugates are significantly more efficient at inhibiting RNA export than are REV NES conjugates, indicating that different NESs may have different abilities to promote protein and RNA export. Surprisingly, an expected control conjugate containing the mutant Rev NES sequence M10 strongly inhibited the export of intronless dihydrofolate reductase mRNA. Nuclear injection of NES peptide conjugates led to mislocalization to the nucleus of 10-20% of the cytoplasmic Ran GTPase-binding protein (RanBP1) indicating that RanBP1 shuttles between the nucleus and the cytoplasm via an NES pathway. These results demonstrate that in vertebrates the export of mRNA, like that of small nuclear RNA, 5S rRNA, and transport factors such as RanBP1, employs NES-mediated molecular machinery.
Adolph,
Role of nonhistone proteins in metaphase chromosome structure.
1977, Pubmed
Adolph,
Role of nonhistone proteins in metaphase chromosome structure.
1977,
Pubmed
Bastos,
Targeting and function in mRNA export of nuclear pore complex protein Nup153.
1996,
Pubmed
Bogerd,
Identification of a novel cellular cofactor for the Rev/Rex class of retroviral regulatory proteins.
1995,
Pubmed
Bogerd,
Protein sequence requirements for function of the human T-cell leukemia virus type 1 Rex nuclear export signal delineated by a novel in vivo randomization-selection assay.
1996,
Pubmed
Dahlberg,
Coupling of nuclear RNA export and protein import in vertebrate cells.
1997,
Pubmed
Fischer,
Diversity in the signals required for nuclear accumulation of U snRNPs and variety in the pathways of nuclear transport.
1991,
Pubmed
,
Xenbase
Fischer,
The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway used by specific cellular RNAs.
1995,
Pubmed
Fornerod,
CRM1 is an export receptor for leucine-rich nuclear export signals.
1997,
Pubmed
,
Xenbase
Fritz,
A human nucleoporin-like protein that specifically interacts with HIV Rev.
1995,
Pubmed
Fritz,
HIV Rev uses a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral RNAs.
1996,
Pubmed
Gerace,
Nuclear export signals and the fast track to the cytoplasm.
1995,
Pubmed
Görlich,
Nucleocytoplasmic transport.
1996,
Pubmed
Grimm,
In vivo selection of RNAs that localize in the nucleus.
1997,
Pubmed
,
Xenbase
Hamm,
Monomethylated cap structures facilitate RNA export from the nucleus.
1990,
Pubmed
,
Xenbase
Iovine,
A nuclear export signal in Kap95p is required for both recycling the import factor and interaction with the nucleoporin GLFG repeat regions of Nup116p and Nup100p.
1997,
Pubmed
Izaurralde,
A role for the M9 transport signal of hnRNP A1 in mRNA nuclear export.
1997,
Pubmed
,
Xenbase
Jarmolowski,
Nuclear export of different classes of RNA is mediated by specific factors.
1994,
Pubmed
,
Xenbase
Kambach,
Intracellular distribution of the U1A protein depends on active transport and nuclear binding to U1 snRNA.
1992,
Pubmed
,
Xenbase
Kim,
Characterization of the nuclear export signal of human T-cell lymphotropic virus type 1 Rex reveals that nuclear export is mediated by position-variable hydrophobic interactions.
1996,
Pubmed
Kutay,
Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor.
1997,
Pubmed
,
Xenbase
Lund,
Nonaqueous isolation of transcriptionally active nuclei from Xenopus oocytes.
1990,
Pubmed
,
Xenbase
Malim,
Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function.
1989,
Pubmed
Malim,
Mutational definition of the human immunodeficiency virus type 1 Rev activation domain.
1991,
Pubmed
Melton,
Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
1984,
Pubmed
Mermer,
Identification of trans-dominant HIV-1 rev protein mutants by direct transfer of bacterially produced proteins into human cells.
1990,
Pubmed
Meyer,
Nuclear transport of human immunodeficiency virus type 1, visna virus, and equine infectious anemia virus Rev proteins: identification of a family of transferable nuclear export signals.
1996,
Pubmed
Meyer,
The HIV-1 Rev trans-activator shuttles between the nucleus and the cytoplasm.
1994,
Pubmed
Michaud,
Multiple pathways in nuclear transport: the import of U2 snRNP occurs by a novel kinetic pathway.
1991,
Pubmed
,
Xenbase
Moore,
The GTP-binding protein Ran/TC4 is required for protein import into the nucleus.
1993,
Pubmed
,
Xenbase
Murphy,
An RNA-export mediator with an essential nuclear export signal.
1996,
Pubmed
Neville,
The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export.
1997,
Pubmed
Pasquinelli,
Reverse 5' caps in RNAs made in vitro by phage RNA polymerases.
1995,
Pubmed
,
Xenbase
Pasquinelli,
The constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV) accesses a cellular mRNA export pathway.
1997,
Pubmed
,
Xenbase
Powers,
The vertebrate GLFG nucleoporin, Nup98, is an essential component of multiple RNA export pathways.
1997,
Pubmed
,
Xenbase
Richards,
A nuclear export signal is essential for the cytosolic localization of the Ran binding protein, RanBP1.
1996,
Pubmed
Saavedra,
Yeast heat shock mRNAs are exported through a distinct pathway defined by Rip1p.
1997,
Pubmed
Saavedra,
The simian retrovirus-1 constitutive transport element, unlike the HIV-1 RRE, uses factors required for cellular mRNA export.
1997,
Pubmed
,
Xenbase
Seedorf,
Importin/karyopherin protein family members required for mRNA export from the nucleus.
1997,
Pubmed
Segref,
Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores.
1997,
Pubmed
Stade,
Exportin 1 (Crm1p) is an essential nuclear export factor.
1997,
Pubmed
Stutz,
A role for nucleoporin FG repeat domains in export of human immunodeficiency virus type 1 Rev protein and RNA from the nucleus.
1996,
Pubmed
,
Xenbase
Stutz,
Identification of a novel nuclear pore-associated protein as a functional target of the HIV-1 Rev protein in yeast.
1995,
Pubmed
Terns,
Retention and 5' cap trimethylation of U3 snRNA in the nucleus.
1994,
Pubmed
,
Xenbase
Terns,
Multiple cis-acting signals for export of pre-U1 snRNA from the nucleus.
1993,
Pubmed
,
Xenbase
Ullman,
Nuclear export receptors: from importin to exportin.
1997,
Pubmed
van Deursen,
G2 arrest and impaired nucleocytoplasmic transport in mouse embryos lacking the proto-oncogene CAN/Nup214.
1996,
Pubmed
Wen,
Identification of a signal for rapid export of proteins from the nucleus.
1995,
Pubmed
Zolotukhin,
Mutations in the nuclear export signal of human ran-binding protein RanBP1 block the Rev-mediated posttranscriptional regulation of human immunodeficiency virus type 1.
1997,
Pubmed
