Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.
RIBOSOMAL FRAMESHIFTING IN RETROVIRAL GENE EXPRESSION
Diss Abstr Int [B]; 49(9):3595 1989. Unique Identifier : AIDSLINE ICDB/90657029 Jacks TE; Univ. of California, San Francisco
Abstract:
In all known retroviruses, the pol gene (which encodes the reverse transcriptase and integrase functions) lies downstream of the gag gene, which codes for the structural proteins of the virus core. In most retroviruses, gag and pol lie in different translational reading frames, either directly overlapping or else with a third gene (pro, encoding the protease) intervening between them and overlapping both. Despite these apparent blocks to continuous translation, all retroviruses express the pol gene by first forming a gag-pol or gag-pro-pol fusion protein. We have used in vitro transcription and translation techniques to help elucidate the mechanism of retroviral pol gene expression. When used to program rabbit reticulocyte lysate translation reactions, in vitro-synthesized mRNA corresponding to the gag-pol domains of either Rous sarcoma virus (RSV) or human immunodeficiency virus yields both gag and gag-pol proteins, indicating that ribosomal frameshifting occurs in the gag-pol overlaps. The frequency of these frameshifting events in vitro (5-10% of translating ribosomes change frame) is high enough to account for gag-pol expression in vivo. A similar experiment using cloned DNA from mouse mammary tumor virus, one of the viruses with an intervening pro gene, demonstrates that two highly efficient frameshifting events occur during expression of this virus's gag-pro-pol protein. Amino acid sequencing and deletion and site-directed mutagenesis, principally with RSV, have suggested that frameshifting in retroviral gene expression requires two features of the mRNA: a site and a structure. The site is the position on the mRNA where the frameshift occurs. It is composed of two short homopolymeric sequences that appear to allow adjacent tRNAs to slip into the alternate (-1) reading frame. The second important feature, a downstream RNA structure, may act by impeding ribosome movement through the frameshift site and thereby allowing increased time for tRNA slippage. While the majority of these experiments were performed on the RSV gag-pol region, similar potential frameshift sites and downstream stem-loop structures exist in other retroviral genes that have been shown to or are believed to permit efficient ribosomal frameshifting. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No AAD88-24673)
Keywords: Animal DNA, Ribosomal/*GENETICS *Gene Expression Regulation, Viral Genes, gag *Genes, pol Mammary Tumor Viruses, Mouse/GENETICS Mice Retroviridae/*GENETICS Sarcoma Viruses, Avian/GENETICS *Transcription, Genetic *Translation, Genetic THESIS 900228
M9020586
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.
