A scientific journey through the 2-5A/RNase L system

Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):381-8. doi: 10.1016/j.cytogfr.2007.06.012. Epub 2007 Jul 27.


The antiviral and antitumor actions of interferons are caused, in part, by a remarkable regulated RNA cleavage pathway known as the 2-5A/RNase L system. 2'-5' linked oligoadenylates (2-5A) are produced from ATP by interferon-inducible synthetases. 2-5A activates pre-existing RNase L, resulting in the cleavage of RNAs within single-stranded regions. Activation of RNase L by 2-5A leads to an antiviral response, although precisely how this happens is a subject of ongoing investigations. Recently, RNase L was identified as the hereditary prostate cancer 1 gene. That finding has led to the discovery of a novel human retrovirus, XMRV. My scientific journey through the 2-5A system recounts some of the highlights of these efforts. Knowledge gained from studies on the 2-5A system could have an impact on development of therapies for important viral pathogens and cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / immunology
  • Cloning, Molecular
  • Endoribonucleases* / genetics
  • Endoribonucleases* / immunology
  • Endoribonucleases* / metabolism
  • Gammaretrovirus / physiology
  • Humans
  • Interferons / immunology
  • Male
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / virology


  • Antiviral Agents
  • Interferons
  • Endoribonucleases
  • 2-5A-dependent ribonuclease