A scientific journey through the 2-5A/RNase L system.
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.
Department of Cancer Biology, NB40 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. silverr@ccf.org
Robert H
RH
Silverman
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology; D003001:Cloning, Molecular; D004722:Endoribonucleases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017988:Gammaretrovirus / Q000502:physiology; D006801:Humans; D007372:Interferons / Q000276:immunology; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000821:virology
D000998:Antiviral Agents; D007372:Interferons; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease