2-5A-dependent ribonuclease; 2-5A-dependent Rnase; ribonuclease 4, IFN-induced; ribonuclease L; Rnase L (RNASEL)

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Function

endoribonuclease
functions in the interferon (IFN) antiviral response
in IFN-treated & virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, & induction of other antiviral genes
RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria & caspase-dependent apoptosis
thus activation of RNASEL could lead to elimination of virus infected cells under some circumstances
might play a central role in the regulation of mRNA
turnover cleaves 3' of UpNp dimers, with preference for UU & UA sequences, to sets of discrete products ranging from between 4 & 22 nucleotides in length
after binding to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) homodimerization & subsequent activation occurs
monomer (inactive) or homodimer (active)

Inhibition:

the nine ankyrin repeats also called 2-5A sensor constitute the N-terminus 2-5A binding domain
the protein kinase domain is predicted to be catalytically inactive; it allows the homodimerization
the ribonuclease domain is located in the C-terminus
- a single active nuclease domain in a dimer is sufficient for ribonuclease activity (putative)
belongs to the protein kinase superfamily
contains 9 ANK repeats
contains 1 KEN domain
contains 1 protein kinase domain

expressed in spleen & thymus > prostate, testis, uterus, small intestine, colon & peripheral blood leukocytes
induced by interferons
- virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins such as 2'-5' oligoadenylate synthetases
- oligoadenylate synthetase is stimulated by dsRNA to produce 5'-phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is to activate RNASEL

defects in RNASEL are a cause of susceptibility to prostate cancer hereditary type 1