RNAse L
Encyclopedia
RNase L is an interferon
-induced ribonuclease
which, upon activation, destroys all RNA
within the cell
(both cellular and viral).
Activation occurs by the following:
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.
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).
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
-induced ribonuclease
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...
which, upon activation, destroys all RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
within the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
(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 cytoplasmCytoplasmThe cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
stimulates 2'-5' oligo(A) synthetaseOAS12'-5'-oligoadenylate synthetase 1 is an enzyme that in humans is encoded by the OAS1 gene.-Further reading:...
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 apoptosisApoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
upon successful viral infection. Degradation of all RNA within the cell (which usually occurs with cessation of translation activity caused by protein kinase R
Protein kinase R
Protein kinase RNA-activated also known as protein kinase R , interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 is an enzyme that in humans is encoded by the EIF2AK2 gene.PKR protects against viral...
) 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):e25Chakrabarti 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).