2′-5′-Oligoadenylate synthetase is activated by a specific RNA sequence motif

Reinhard Kodym, Elisabeth Kodym, Michael D. Story

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

2′-5′-Oligoadenylate synthetase plays a central role in the cellular innate antiviral response. Although activation of 2′-5′-oligoadenylate synthetase by double stranded RNA was discovered more than 30 years ago it is still unclear which sequence features are required by an RNA to activate the enzyme. A pool of chemically synthesized short double stranded RNAs of specific sequence was used to probe 2′-5′-oligoadenylate synthetase activation. It was found that activating double stranded RNAs contain the following motif: NNWWNNNNNNNNNWGN. Verification of this sequence motif in a pool of 102 small double stranded RNAs demonstrated a false positive prediction rate of 8% and a false negative prediction rate of 12%. The sequence motif identified provides mechanistic insight into the mechanism of 2′-5′-oligoadenylate synthetase activation by double stranded RNA and allows theoretical predictions whether a given RNA molecule has the capability to activate 2′-5′-oligoadenylate synthetase.

Original languageEnglish (US)
Pages (from-to)317-322
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume388
Issue number2
DOIs
StatePublished - Oct 16 2009

Keywords

  • 2′-5′-Oligoadenylate
  • Double stranded RNA
  • RNA A-helix
  • Ribonuclease L
  • siRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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