Document 0793
 DOCN  M9590793
 TI    Efficiency of reinitiation of translation on human immunodeficiency
       virus type 1 mRNAs is determined by the length of the upstream open
       reading frame and by intercistronic distance.
 DT    9509
 AU    Luukkonen BG; Tan W; Schwartz S; Microbiology and Tumorbiology Center,
       Karolinska Institute,; Stockholm, Sweden.
 SO    J Virol. 1995 Jul;69(7):4086-94. Unique Identifier : AIDSLINE
       MED/95287458
 AB    In this study, we examined the mechanism of translation of the human
       immunodeficiency virus type 1 tat mRNA in eucaryotic cells. This mRNA
       contains the tat open reading frame (ORF), followed by rev and nef ORFs,
       but only the first ORF, encoding tat, is efficiently translated.
       Introduction of premature stop codons in the tat ORF resulted in
       efficient translation of the downstream rev ORF. We show that the degree
       of inhibition of translation of rev is proportional to the length of the
       upstream tat ORF. An upstream ORF spanning 84 nucleotides was predicted
       to inhibit 50% of the ribosomes from initiating translation at
       downstream AUGs. Interestingly, the distance between the upstream ORF
       and the start codon of the second ORF also played a role in efficiency
       of downstream translation initiation. It remains to be investigated if
       these conclusions relate to translation of mRNAs other than human
       immunodeficiency virus type 1 mRNAs. The strong inhibition of rev
       translation exerted by the presence of the tat ORF may reflect the
       different roles of Tat and Rev in the viral life cycle. Tat acts early
       to induce high production of all viral mRNAs. Rev induces a switch from
       the early to the late phase of the viral life cycle, resulting in
       production of viral structural proteins and virions. Premature Rev
       production may result in entrance into the late phase in the presence of
       suboptimal levels of viral mRNAs coding for structural proteins,
       resulting in inefficient virus production.
 DE    Base Sequence  Gene Products, rev/BIOSYNTHESIS/GENETICS  Gene Products,
       tat/*GENETICS  Genes, Structural  HIV-1/*GENETICS  Molecular Sequence
       Data  *Open Reading Frames  RNA, Viral/*METABOLISM  Support, Non-U.S.
       Gov't  *Translation, Genetic  JOURNAL ARTICLE

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