Abstract
The 2′,5′-oligoadenylate-dependent ribonuclease L (RNase L) is central to the innate cellular defense mechanism induced by type I interferons during intracellular infection. The protein, activated by 2′,5′-oligoadenylates, precludes the replication of the infectious agent by cleaving single-stranded RNA and, along with the double-stranded RNA-dependent protein kinase, its spreading by inducing the cell to undergo suicide (apoptosis). In absence of infection, the protein remains dormant. Recent evidence indicates, however, that the protein is activated in absence of infection and may play a role in cell differentiation, immune activation, and act as a tumor-suppressor. A deregulation in this pathway has been documented in immune cells of chronic fatigue syndrome patients which involves the presence of a catalytically active truncated RNase L. This protein escapes the normal regulation which implies the development of a cascade of unwanted cellular events. The present article reviews our current understanding of this deregulation, enlightens its relevance in the pathological process and proposes new targets for therapeutic development.