Document 0048
 DOCN  M9470048
 TI    Presence of negative and positive cis-acting RNA splicing elements
       within and flanking the first tat coding exon of human immunodeficiency
       virus type 1.
 DT    9409
 AU    Amendt BA; Hesslein D; Chang LJ; Stoltzfus CM; Department of
       Microbiology, University of Iowa, Iowa City 52242.
 SO    Mol Cell Biol. 1994 Jun;14(6):3960-70. Unique Identifier : AIDSLINE
       MED/94254853
 AB    The human immunodeficiency virus type 1 (HIV-1) RNA follows a complex
       splicing pathway in which a single primary transcript either remains
       unspliced or is alternatively spliced to more than 30 different singly
       and multiply spliced mRNAs. We have used an in vitro splicing assay to
       identify cis elements within the viral genome that regulate HIV-1 RNA
       splicing. A novel splicing regulatory element (SRE) within the first tat
       coding exon has been detected. This element specifically inhibits
       splicing at the upstream 3' splice site flanking this tat exon. The
       element only functions when in the sense orientation and is position
       dependent when inserted downstream of a heterologous 3' splice site. In
       vivo, an HIV-1 SRE mutant demonstrated a decrease in unspliced viral
       RNA, increased levels of single- and double-spliced tat mRNA, and
       reduced levels of env and rev mRNAs. In addition to the negative
       cis-acting SRE, the flanking 5' splice site downstream of the first tat
       coding exon acts positively to increase splicing at the upstream 3'
       splice sites. These results are consistent with hypotheses of bridging
       interactions between cellular factors that bind to the 5' splice site
       and those that bind at the upstream 3' splice site.
 DE    *Alternative Splicing  Base Sequence  Cell Nucleus/METABOLISM  DNA
       Primers  *Exons  Gene Expression Regulation, Viral  *Genes, tat  Hela
       Cells  Human  HIV-1/*GENETICS/METABOLISM  Molecular Sequence Data
       Mutagenesis  Polymerase Chain Reaction  Regulatory Sequences, Nucleic
       Acid  Restriction Mapping  *RNA Splicing  RNA, Messenger/*BIOSYNTHESIS
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Transfection
       JOURNAL ARTICLE

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