A novel RNA molecular signature for activation of 2'-5' oligoadenylate synthetase-1

Nucleic Acids Res. 2015 Jan;43(1):544-52. doi: 10.1093/nar/gku1289. Epub 2014 Dec 4.


Human 2'-5' oligoadenylate synthetase-1 (OAS1) is central in innate immune system detection of cytoplasmic double-stranded RNA (dsRNA) and promotion of host antiviral responses. However, the molecular signatures that promote OAS1 activation are currently poorly defined. We show that the 3'-end polyuridine sequence of viral and cellular RNA polymerase III non-coding transcripts is critical for their optimal activation of OAS1. Potentiation of OAS1 activity was also observed with a model dsRNA duplex containing an OAS1 activation consensus sequence. We determined that the effect is attributable to a single appended 3'-end residue, is dependent upon its single-stranded nature with strong preference for pyrimidine residues and is mediated by a highly conserved OAS1 residue adjacent to the dsRNA binding surface. These findings represent discovery of a novel signature for OAS1 activation, the 3'-single-stranded pyrimidine (3'-ssPy) motif, with potential functional implications for OAS1 activity in its antiviral and other anti-proliferative roles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / chemistry
  • 2',5'-Oligoadenylate Synthetase / genetics
  • 2',5'-Oligoadenylate Synthetase / metabolism*
  • Enzyme Activation
  • Humans
  • Mutagenesis
  • Nucleotide Motifs
  • Pyrimidines / analysis
  • RNA, Double-Stranded / metabolism
  • RNA, Untranslated / chemistry
  • RNA, Untranslated / metabolism
  • RNA, Viral / chemistry*
  • RNA, Viral / metabolism


  • Pyrimidines
  • RNA, Double-Stranded
  • RNA, Untranslated
  • RNA, Viral
  • OAS1 protein, human
  • 2',5'-Oligoadenylate Synthetase