RNase L

RNase L (Latent) is an interferon-induced ribonuclease which, upon activation, destroys all RNA within the cell (both cellular and viral).

Production and Activation
RNase L is present in very minute quantities during the normal cell cycle. When interferon binds to cell receptors, it activates transcription of around 300 genes to bring about the antiviral state. Among the enzymes produced is RNase L, which is initially in an inactive form.

Activation occurs by the following:
 * (1) dsRNA in the cytoplasm stimulates 2'-5' oligo(A) synthetase to produce strands of 2'-5' adenylic acid (versus the normal 3'-5'; ATP-dependent);
 * (2) these strands induce activation of RNase L which then forms a dimer and proceeds to degrade all RNA within the cell.

Purpose
RNase L is part of the body's innate immune defense, namely the antiviral state of the cell. When a cell is in the antiviral state, it is highly resistant to viral attacks and is also ready to undergo apoptosis upon successful viral infection. Degradation of all RNA within the cell (which usually occurs with cessation of translation activity caused by protein kinase R) is the cell's last stand against a virus before it attempts apoptosis. Interferon beta is produced in response to the small RNA cleavage products produced by RNase L during viral infections.

Literature
Urisman A, Molinaro RJ, Fisher N, et al. (2006) Identification of a novel gammaretrovirus in prostate tumours of patients homozygous R462Q for RNaseL variant. PLos pathog. 2(3):e25

Chakrabarti A, Jha BK, Silverman RH. (2011) New Insights into the Role of RNase L in Innate Immunity. Journal of Interferon and Cytokine Research. 31(1).

RNase L