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M94A0295.TXT
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1994-10-08
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Document 0295
DOCN M94A0295
TI Evidence that HIV-1 Rev directly promotes the nuclear export of
unspliced RNA.
DT 9412
AU Fischer U; Meyer S; Teufel M; Heckel C; Luhrmann R; Rautmann G; Institut
fur Molekularbiologie und Tumorforschung, Marburg,; Germany.
SO EMBO J. 1994 Sep 1;13(17):4105-12. Unique Identifier : AIDSLINE
MED/94357184
AB The Rev trans-activator of human immunodeficiency virus type 1 (HIV-1)
is a protein that regulates the simultaneous appearance in the cytoplasm
of both spliced and unspliced forms of viral mRNAs from the same viral
transcripts by way of recognition of a target sequence termed the
Rev-responsive element (RRE). Whether Rev acts directly on RNA export or
by inhibition of splicing, or both, is still a matter of debate. We have
addressed this issue in Xenopus laevis oocytes by microinjecting RNA
molecules containing RRE along with purified recombinant Rev protein
into the oocyte nuclei. Adenovirus pre-mRNA containing an RRE in the
intron was spliced equally well in the absence and presence of Rev
protein. Only in the presence of Rev was non-spliced pre-mRNA exported
from the nucleus; more surprisingly, the excised intron lariat
(containing RRE) was also exported. Furthermore, an RRE-containing mRNA
molecule that lacked intron sequences was also efficiently exported from
the nucleus in a Rev-dependent manner. Therefore our results demonstrate
that Rev can act directly at the level of nuclear export, independent of
any inhibitory effect that it may exert on the splicing of pre-mRNA.
Finally, our finding that the Rev mutant M10, shown previously to be
inactive in human lymphoid cells, was also unable to export
RRE-containing RNA molecules from oocyte nuclei suggests that one or
more cellular factors, evolutionarily conserved between humans and
Xenopus, interact with Rev in both cell systems to promote nuclear RNA
export.
DE Animal Base Sequence Biological Transport Cell Nucleus/*METABOLISM
Exons/GENETICS Gene Products, rev/GENETICS/*METABOLISM Genes,
Synthetic HIV-1/*GENETICS Microinjections Molecular Sequence Data
Mutation Oocytes Protein Binding Recombinant Proteins/METABOLISM RNA
Precursors/GENETICS/*METABOLISM *RNA Splicing RNA-Binding
Proteins/METABOLISM Sequence Deletion Support, Non-U.S. Gov't Xenopus
laevis JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).