Document 0596
 DOCN  M9490596
 TI    A basis for new approaches to the chemotherapy of AIDS: novel genes in
       HIV-1 potentially encode selenoproteins expressed by ribosomal
       frameshifting and termination suppression.
 DT    9411
 AU    Taylor EW; Ramanathan CS; Jalluri RK; Nadimpalli RG; Computational
       Center for Molecular Structure and Design,; University of Georgia,
       Athens 30602-2352.
 SO    J Med Chem. 1994 Aug 19;37(17):2637-54. Unique Identifier : AIDSLINE +
 AB    Several previously unnoticed genes in the human immunodeficiency virus
       type 1 (HIV-1), potentially encoding selenoproteins, have been
       discovered by analyzing the genomic RNA structure and its relation to
       novel open reading frames. We have found a number of new potential RNA
       pseudoknots, including one in the long terminal repeat, several that
       coincide with highly conserved enzyme active site sequences in the pol
       coding region, and one in the env coding region. These pseudoknots can
       potentially direct the synthesis of selenocysteine (SeC) containing--1
       frameshift fusion proteins. This is possible because we have found
       potential SeC insertion sequences (SECIS) in the RNA of HIV and other
       retroviruses; such structures are known to be necessary and sufficient
       for the incorporation of SeC at UGA stop codons anywhere in a eukaryotic
       mRNA. In several locations, UGA codons in the -1 reading frame are
       highly conserved across a broad spectrum of primate immunodeficiency
       viruses. Due to the degeneracy of the genetic code, this conservation
       cannot be explained by evolutionary selection of the pol gene protein
       sequence alone. Such observations, combined with the conservation of the
       associated reading frames, strongly suggest that these are real genes,
       and thus that the pseudoknots are also real. A protease
       pseudoknot-directed -1 frameshift fusion protein contains a highly
       conserved SeC codon and has significant similarities to a number of DNA
       binding proteins, including papillomavirus E2 proteins, suggesting it
       may be a virally encoded repressor of HIV transcription when cleaved by
       protease from the rest of the gag-pol gene product. A reverse
       transcriptase (RT) frameshift fusion protein replaces the RT active site
       with a highly conserved SeC-containing module. An integrase frameshift
       fusion protein contains the N-terminal integrase DNA-binding domain and
       a potential ATP-binding GKS motif; it has significant similarities to
       several helicases, but no SeC codons. A potential frameshift fusion
       protein from env has one SeC codon, but not in a highly conserved
       position. SeC incorporation could extend the nef gene product by 33
       residues through the C-terminal UGA codon without frameshifting,
       potentially leading to substantial SeC utilization in infected
       cells.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY  Amino Acid Sequence
       Antiviral Agents/*CHEMICAL SYNTHESIS  Base Sequence  Codon  Comparative
       Study  Conserved Sequence  Drug Design  DNA
       Nucleotidyltransferases/BIOSYNTHESIS  DNA-Binding Proteins/BIOSYNTHESIS
       *Frameshift Mutation  *Genes, pol  *Genes, Viral  Human  *HIV Long
       Terminal Repeat  HIV-1/DRUG EFFECTS/*GENETICS  Molecular Sequence Data
       Nucleic Acid Conformation  Proteins/*BIOSYNTHESIS  Reading Frames
       Recombinant Fusion Proteins/BIOSYNTHESIS  Ribosomes/METABOLISM  RNA,
       Messenger/BIOSYNTHESIS/CHEMISTRY  RNA, Viral/*BIOSYNTHESIS/CHEMISTRY
       Sequence Homology, Amino Acid  Support, U.S. Gov't, P.H.S.  Suppression,
       Genetic  Viral Proteins/*BIOSYNTHESIS/GENETICS  JOURNAL ARTICLE

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