       Document 0393
 DOCN  M9630393
 TI    Poly(A) site selection in the HIV-1 provirus: inhibition of
       promoter-proximal polyadenylation by the downstream major splice donor
       site.
 DT    9603
 AU    Ashe MP; Griffin P; James W; Proudfoot NJ; Sir William Dunn School of
       Pathology, University of Oxford, UK.
 SO    Genes Dev. 1995 Dec 1;9(23):3008-25. Unique Identifier : AIDSLINE
       MED/96101599
 AB    In common with all retroviruses, the human immunodeficiency virus type 1
       (HIV-1) contains duplicated long terminal repeat (LTR) sequences
       flanking the proviral genome. These LTRs contain identical poly(A)
       signals, which are both transcribed into RNA. Therefore, to allow
       efficient viral expression, a mechanism must exist to either restrict
       promoter-proximal poly(A) site use or enhance the activity of the
       promoter-distal poly(A) site. We have examined the use of both poly(A)
       sites using proviral clones. Mutation of the previously defined upstream
       activatory sequences of the 3' LTR poly(A) site decreases the efficiency
       of polyadenylation when placed in competition with an efficient
       downstream processing signal. However, in the absence of competition,
       these mutations have no effect on HIV-1 polyadenylation. In addition,
       the 5' LTR poly(A) site is inactive, whereas a heterologous poly(A) site
       positioned in its place is utilized efficiently. Furthermore,
       transcription initiating from the 3' LTR promoter utilizes the 3' LTR
       poly(A) signal efficiently. Therefore, the main determinant of the
       differential poly(A) site use appears to be neither proximity to a
       promoter element in the 5' LTR nor the presence of upstream activating
       sequences at the 3' LTR. Instead, we show that the major splice donor
       site that is immediately downstream of the 5' LTR inhibits cleavage and
       polyadenylation at the promoter-proximal site. The fact that this
       poly(A) site is active in a proviral clone when the major splice donor
       site is mutated suggests that the selective use of poly(A) signals in
       HIV-1 is mediated by a direct inhibition of the HIV-1 poly(A) site by
       downstream splicing events or factors involved in splicing.
 DE    Base Sequence  Binding, Competitive  Gene Expression Regulation  Human
       HIV Long Terminal Repeat/*GENETICS  HIV-1/*GENETICS  Molecular Sequence
       Data  Mutation  *Poly A  Promoter Regions (Genetics)
       Proviruses/*GENETICS  *RNA Splicing  *RNA, Messenger  Support, Non-U.S.
       Gov't  Transcription, Genetic  JOURNAL ARTICLE

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

