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

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