New insights into the role of RNase L in innate immunity

J Interferon Cytokine Res. 2011 Jan;31(1):49-57. doi: 10.1089/jir.2010.0120. Epub 2010 Dec 29.


The interferon (IFN)-inducible 2'-5'-oligoadenylate synthetase (OAS)/RNase L pathway blocks infections by some types of viruses through cleavage of viral and cellular single-stranded RNA. Viruses induce type I IFNs that initiate signaling to the OAS genes. OAS proteins are pathogen recognition receptors for the viral pathogen-associated molecular pattern, double-stranded RNA. Double-stranded RNA activates OAS to produce p(x)5'A(2'p5'A)(n); x = 1-3; n > 2 (2-5A) from ATP. Upon binding 2-5A, RNase L is converted from an inactive monomer to a potently active dimeric endoribonuclease for single-stranded RNA. RNase L contains, from N- to C-terminus, a series of 9 ankyrin repeats, a linker, several protein kinase-like motifs, and a ribonuclease domain homologous to Ire1 (involved in the unfolded protein response). In the past few years, it has become increasingly apparent that RNase L and OAS contribute to innate immunity in many ways. For example, small RNA cleavage products produced by RNase L during viral infections can signal to the retinoic acid-inducible-I like receptors to amplify and perpetuate signaling to the IFN-β gene. In addition, RNase L is now implicated in protecting the central nervous system against viral-induced demyelination. A role in tumor suppression was inferred by mapping of the RNase L gene to the hereditary prostate cancer 1 (HPC1) gene, which in turn led to discovery of the xenotropic murine leukemia-related virus. A broader role in innate immunity is suggested by involvement of RNase L in cytokine induction and endosomal pathways that suppress bacterial infections. These newly described findings about RNase L could eventually provide the basis for developing broad-spectrum antimicrobial drugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics
  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Animals
  • Antigens, Surface / metabolism
  • Demyelinating Diseases / prevention & control
  • ELAV Proteins
  • ELAV-Like Protein 1
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism*
  • Gene Expression Regulation
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate*
  • Interferons / genetics
  • Interferons / metabolism
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Protein Interaction Domains and Motifs
  • RNA, Double-Stranded / metabolism
  • RNA, Messenger / metabolism
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Virus Diseases / immunology
  • Virus Diseases / metabolism


  • Antigens, Surface
  • ELAV Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • RNA, Double-Stranded
  • RNA, Messenger
  • RNA, Viral
  • RNA-Binding Proteins
  • Interferons
  • 2',5'-Oligoadenylate Synthetase
  • Endoribonucleases
  • 2-5A-dependent ribonuclease