       Document 0061
 DOCN  M95B0061
 TI    Presence of exon splicing silencers within human immunodeficiency virus
       type 1 tat exon 2 and tat-rev exon 3: evidence for inhibition mediated
       by cellular factors.
 DT    9511
 AU    Amendt BA; Si ZH; Stoltzfus CM; Department of Microbiology, University
       of Iowa, Iowa City 52242,; USA.
 SO    Mol Cell Biol. 1995 Aug;15(8):4606-15. Unique Identifier : AIDSLINE
       MED/95349628
 AB    Human immunodeficiency virus type 1 (HIV-1) pre-mRNA splicing is
       regulated in order to maintain pools of unspliced and partially spliced
       viral RNAs as well as the appropriate levels of multiply spliced mRNAs
       during virus infection. We have previously described an element in tat
       exon 2 that negatively regulates splicing at the upstream tat 3' splice
       site 3 (B. A. Amendt, D. Hesslein, L.-J. Chang, and C. M. Stoltzfus,
       Mol. Cell. Biol. 14:3960-3970, 1994). In this study, we further defined
       the element to a 20-nucleotide (nt) region which spans the C-terminal
       vpr and N-terminal tat coding sequences. By analogy with exon splicing
       enhancer (ESE) elements, we have termed this element an exon splicing
       silencer (ESS). We show evidence for another negative cis-acting region
       within tat-rev exon 3 of HIV-1 RNA that has sequence motifs in common
       with a 20-nt ESS element in tat exon 2. This sequence is juxtaposed to a
       purine-rich ESE element to form a bipartite element regulating splicing
       at the upstream tat-rev 3' splice site. Inhibition of the splicing of
       substrates containing the ESS element in tat exon 2 occurs at an early
       stage of spliceosome assembly. The inhibition of splicing mediated by
       the ESS can be specifically abrogated by the addition of competitor RNA.
       Our results suggest that HIV-1 RNA splicing is regulated by cellular
       factors that bind to positive and negative cis elements in tat exon 2
       and tat-rev exon 3.
 DE    Amino Acid Sequence  Base Sequence  Binding, Competitive  Exons/GENETICS
       *Gene Expression Regulation, Viral  Gene Products,
       rev/BIOSYNTHESIS/*GENETICS  Gene Products, tat/BIOSYNTHESIS/*GENETICS
       HIV-1/*GENETICS  Models, Genetic  Molecular Sequence Data  Regulatory
       Sequences, Nucleic Acid/GENETICS  *RNA Splicing  RNA,
       Messenger/METABOLISM  RNA, Viral/METABOLISM  Spliceosomes/METABOLISM
       Substrate Specificity  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

