The human 2'-5'oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2'-5' instead of 3'-5' phosphodiester bond formation

Biochimie. Jun-Jul 2007;89(6-7):779-88. doi: 10.1016/j.biochi.2007.02.003. Epub 2007 Feb 20.

Abstract

The demonstration by Kerr and colleagues that double-stranded (ds) RNA inhibits drastically protein synthesis in cell-free systems prepared from interferon-treated cells, suggested the existence of an interferon-induced enzyme, which is dependent on dsRNA. Consequently, two distinct dsRNA-dependent enzymes were discovered: a serine/threonine protein kinase that nowadays is referred to as PKR and a 2'-5'oligoadenylate synthetase (2'-5'OAS) that polymerizes ATP to 2'-5'-linked oligomers of adenosine with the general formula pppA(2'p5'A)(n), n>or=1. The product is pppG2'p5'G when GTP is used as a substrate. Three distinct forms of 2'-5'OAS exist in human cells, small, medium, and large, which contain one, two, and three OAS units, respectively, and are encoded by distinct genes clustered on the 2'-5'OAS locus on human chromosome 12. OASL is an OAS like IFN-induced protein encoded by a gene located about 8 Mb telomeric from the 2'-5'OAS locus. OASL is composed of one OAS unit fused at its C-terminus with two ubiquitin-like repeats. The human OASL is devoid of the typical 2'-5'OAS catalytic activity. In addition to these structural differences between the various OAS proteins, the three forms of 2'-5'OAS are characterized by different subcellular locations and enzymatic parameters. These findings illustrate the apparent structural and functional complexity of the human 2'-5'OAS family, and suggest that these proteins may have distinct roles in the cell.

Publication types

  • Review

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / chemistry*
  • 2',5'-Oligoadenylate Synthetase / physiology*
  • Animals
  • Catalysis
  • Catalytic Domain
  • Chromosomes, Human, Pair 12 / chemistry
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / chemistry
  • Interferons / chemistry
  • Interferons / metabolism*
  • Models, Biological
  • Models, Genetic
  • Multigene Family
  • Protein Structure, Tertiary
  • RNA, Double-Stranded / chemistry
  • Recombinant Proteins
  • Ubiquitin / chemistry

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Double-Stranded
  • Recombinant Proteins
  • Ubiquitin
  • Interferons
  • 2',5'-Oligoadenylate Synthetase