       Document 0062
 DOCN  M95B0062
 TI    Identification of positive and negative splicing regulatory elements
       within the terminal tat-rev exon of human immunodeficiency virus type 1.
 DT    9511
 AU    Staffa A; Cochrane A; Department of Microbiology and Immunology, McGill
       University,; Montreal, Quebec, Canada.
 SO    Mol Cell Biol. 1995 Aug;15(8):4597-605. Unique Identifier : AIDSLINE
       MED/95349627
 AB    The requirement of human immunodeficiency virus type 1 to generate
       numerous proteins from a single primary transcript is met largely by the
       use of suboptimal splicing to generate over 30 mRNAs. To ensure that
       appropriate quantities of each protein are produced, there must be a
       signal(s) that controls the efficiency with which any particular splice
       site in the RNA is used. To identify this control element(s) and to
       understand how it operates to generate the splicing pattern observed, we
       have initially focused on the control of splicing of the tat-rev intron,
       which spans the majority of the env open reading frame. Previous
       analysis indicated that a suboptimal branchpoint and polypyridimine
       tract in this intron contribute to its suboptimal splicing (A. Staffa
       and A. Cochrane, J. Virol. 68:3071-3079, 1994). In this report, we
       identify two additional elements within the 3'-terminal exon, an
       exon-splicing enhancer (ESE) and an exon splicing silencer (ESS), that
       modulate the overall efficiency with which the 3' tat-rev splice site is
       utilized. Both elements are capable of functioning independently of one
       another. Furthermore, while both the ESE and ESS can function in a
       heterologous context, the function of the ESS is extremely sensitive to
       the sequence context into which it is placed. In conclusion, it would
       appear that the presence of a suboptimal branchpoint and a
       polypyrimidine tract as well as the ESE and ESS operate together to
       yield the balanced splicing of the tat-rev intron observed in vivo.
 DE    Animal  Base Composition  Base Sequence  Cells, Cultured
       Exons/*GENETICS  Gene Expression Regulation, Viral  Gene Products,
       rev/BIOSYNTHESIS/*GENETICS  Gene Products, tat/BIOSYNTHESIS/*GENETICS
       HIV-1/*GENETICS  Molecular Sequence Data  Mutagenesis  Regulatory
       Sequences, Nucleic Acid/GENETICS  *RNA Splicing  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

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

