Thursday, June 21, 2012

2’,5’-oligoadenylate synthetase-ribonuclease L system attacks viral RNA

 Double strand RNAs (dsRNAs) induce interferons (IFNs) in mammalian cells. dsRNAs are produced by the replication of RNA viruses in infected cells, and are detected by cellular innate immune sensors, which leading to the secretion of IFNs. The released IFNs send signals to the neighboring cells, where many interferon-stimulated genes (ISGs) are induced.
 One of the most known ISGs is 2’,5’-oligoadenylate synthetase-ribonuclease L (OAS-RNase L) pathway. OAS is activated by de novo infected viral dsRNAs, and then it synthesizes 2’,5’-linked oligoadenylates (2-5A), which differs from normal nucleic acids such as DNA and RNA that have 3’,5’-link, by using ATPs as substrates. 2-5A binds to RNase L, causing inactive RNase L monomers to form activated dimers. The activated RNase L dimmers cleave viral RNAs, which results in the inhibition of the viral propagation.

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