2'-5'-Oligoadenylate synthetase is activated by a specific RNA sequence motif.
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.
Kodym
Reinhard
R
Division of Molecular Radiation Biology, Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX 75390-9187, USA. reinhard.kodym@utsouthwestern.edu
Kodym
Elisabeth
E
Story
Michael D
MD
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D006801:Humans; D009690:Nucleic Acid Conformation; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism*; D017423:Sequence Analysis, RNA
D012330:RNA, Double-Stranded; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase