A discrete element 3' of human immunodeficiency virus 1 (HIV-1) and HIV-2 mRNA initiation sites mediates transcriptional activation by an HIV trans activator

Journal Article · Wed Jun 01 04:00:00 EDT 1988 · Mol. Cell. Biol.; (United States)

DOI:https://doi.org/10.1128/MCB.8.6.2555· OSTI ID:7188619

Jakobovits, A; Smith, D H; Jakobovits, E B; Capon, D J

An important point of regulation in the reproductive growth and latency of the human and simian immunodeficiency viruses (HIV and SIV, respectively) is provided by virally encoded trans-activators (tat), proteins capable of dramatically increasing viral gene expression. The mechanism of this autostimulatory pathway has remained unclear, however, with substantial effects having been reported at the level of either mRNA accumulation, translational efficiency, or both. The authors' previous findings indicated that trans-activation results primarily from induction of RNA levels but could not distinguish between the roles of transcriptional rate, RNA stabilization, and RNA transport in this event. In addition, the boundaries of tat-responding elements, which would be valuable in elucidating the mode of tat action, are not precisely known. In this study, HIV-1 and HIV-2 long terminal repeat-directed expression was characterized by using in an vitro nuclear transcription assay to clarify this mechanism, and a detailed mutational analysis was undertaken to localize precisely the sequences participating in this process. Two key findings were revealed: an increased transcription rate was the primary event in tat-mediated activation of HIV-1 and HIV-2, and trans-activation was impaired by mutations in two regions, the TATA box and sequences between +19 to +42, a region lacking enhancer activity. These results implicate a discrete 3' regulatory element in the transcriptional activation of the HIVs.

• Research Organization: Dept. of Molecular Biology, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, CA (US)
• OSTI ID: 7188619
• Journal Information: Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 8:6; ISSN MCEBD
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
550400 -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AIDS VIRUS
BIOLOGICAL PATHWAYS
CELL TRANSFORMATIONS
GENE MUTATIONS
GENE OPERONS
GENE REGULATION
IMMUNOSUPPRESSION
MESSENGER-RNA
MICROORGANISMS
MOLECULAR BIOLOGY
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PARASITES
RNA
RNA PROCESSING
SIMIAN VIRUS
VIRUSES