Ribonuclease L

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Ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent)
Protein RNASEL PDB 1wdy.png
PDB rendering based on 1wdy.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols RNASEL ; PRCA1; RNS4
External IDs OMIM180435 MGI1098272 HomoloGene8040 ChEMBL: 3575 GeneCards: RNASEL Gene
EC number 3.1.26.-, 3.1.27.-
RNA expression pattern
PBB GE RNASEL 221287 at tn.png
More reference expression data
Species Human Mouse
Entrez 6041 24014
Ensembl ENSG00000135828 ENSMUSG00000066800
UniProt Q05823 Q05921
RefSeq (mRNA) NM_021133 NM_011882
RefSeq (protein) NP_066956 NP_036012
Location (UCSC) Chr 1:
182.54 – 182.56 Mb
Chr 1:
153.75 – 153.76 Mb
PubMed search [1] [2]

Ribonuclease L or RNase L (for latent), known sometimes as ribonuclease 4 or 2-5A-dependent ribonuclease — is an interferon-induced ribonuclease which, upon activation, destroys all RNA within the cell (both cellular and viral). RNase L is an enzyme that in humans is encoded by the RNASEL gene.[1]

This gene encodes a component of the interferon-regulated 2-5A system that functions in the antiviral and antiproliferative roles of interferons.

Synthesis and activation[edit]

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.


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.

Clinical significance[edit]

Mutations in this gene have been associated with predisposition to prostate cancer and this gene is a candidate for the hereditary prostate cancer 1 (HPC1) allele.[2] In 2002, the “hereditary prostate cancer 1” locus (HPC1) was mapped to the RNase L gene, implicating it in the development of prostate cancer.[3]

Impairments of the 2'-5' oligoadenylate (2-5 A) synthetase/RNase L pathway in chronic fatigue syndrome (CFS) have been investigated.[4][5]


  1. ^ Squire J, Zhou A, Hassel BA, Nie H, Silverman RH (Jun 1994). "Localization of the interferon-induced, 2-5A-dependent RNase gene (RNS4) to human chromosome 1q25". Genomics 19 (1): 174–5. doi:10.1006/geno.1994.1033. PMID 7514564. 
  2. ^ "Entrez Gene: RNASEL ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent)". 
  3. ^ Carpten J, Nupponen N, Isaacs S, et al. (February 2002). "Germline mutations in the ribonuclease L gene in families showing linkage with HPC1". Nature Genetics 30 (2): 181–4. doi:10.1038/ng823. PMID 11799394. 
  4. ^ Nijs J, De Meirleir K (Nov–Dec 2005). "Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue syndrome". In Vivo 19 (6): 1013–21. PMID 16277015. 
  5. ^ Suhadolnik RJ et al (1997). "Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome". J Interferon Cytokine Res 17 (7): 377–85. doi:10.1089/jir.1997.17.377. PMID 9243369. 

Further reading[edit]

External links[edit]