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M9471070.TXT
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1994-08-09
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Document 1070
DOCN M9471070
TI Function of the human T-cell leukemia virus Rex response element in
viral RNA processing.
DT 9409
AU Ahmed YF; Duke Univ.
SO Diss Abstr Int [B]; 53(12):6110 1993. Unique Identifier : AIDSLINE
ICDB/94696128
AB The type I human T cell leukemia virus (HTLV-I) is the etiologic agent
of an aggressive malignancy of human CD4+ T lymphocytes known as adult T
cell leukemia. In addition to the gag, pol and env genes present in all
replication-competent retroviruses, HTLV contains two additional
regulatory genes tax and rex. The HTLV-I Rex protein functions at a
post-transcriptional level to augment the cytoplasmic expression of the
unspliced and singly spliced viral mRNA species that encode the gag,
pol, and env gene products. The action of Rex requires a large
cis-regulatory RNA sequence present in all viral transcripts termed the
Rex response element (RexRE). Using a mutational analysis of the RexRE,
we delineate 7 nucleotides of the 255 nucleotide element that appear to
be critical contact points for the Rex protein. These nucleotides are
located directly on opposing sides of a stem-like subregion within the
element that is predicted by computer modeling. Substitution mutations
within this subregion decrease the binding of Rex to its response
element and thereby decrease the in vivo Rex response. Rex action
requires both the overall secondary structure intrinsic to the RexRE,
and these seven specific nucleotides in one stem-like subregion. In
addition to regulating structural gene expression, the RexRE plays a
critical role in the polyadenylation of all HTLV-I mRNA transcripts in a
manner that is independent of Rex. Specifically, folding of the RexRE
serves to spatially juxtapose the distantly separated AAUAAA hexamer
sequence and the GU-rich element located downstream of the cleavage site
thereby allowing 3' processing to occur. Studies employing an in vitro
assay of polyadenylation have revealed that folding of the RexRE is
essential for the cooperative and stable binding of two enriched nuclear
factors at the upstream hexamer sequence and the downstream GU-rich
element which in turn commits this viral poly A site to 3' processing.
Thus using a twist on the standard tricks utilized by retroviruses,
HTLV-I employs a single cis-acting highly structured RNA element to deal
with two problems specific to retroviral RNA processing. (Full text
available from University Microfilms International, Ann Arbor, MI, as
Order No. AAD93-12365)
DE Gene Products, rex/*GENETICS Gene Products, tax/*GENETICS Human
Leukemia, T-Cell/*GENETICS RNA Splicing RNA, Messenger/GENETICS RNA,
Viral/GENETICS Transcription, Genetic THESIS
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).