Activation of interferon-inducible 2'-5' oligoadenylate synthetase by adenoviral VAI RNA

Shailesh Y. Desai, Rekha C. Patel, Ganes C. Sen, Pawan Malhotra, Ghanashyam D. Ghadge, Bayar Thimmapaya

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

2'-5' oligoadenylate (2-5(A)) synthetase and protein kinase, RNA activated (PKR) are the only two known enzymes that bind double-stranded RNA (dsRNA) and get activated by it. We have previously identified their dsRNA binding domains, which do not have any sequence homology. Here, we report a profound difference between the two enzymes with respect to the structural features of the dsRNA that are required for their activation. The adenoviral virus- associated type I (VAI) RNA cannot activate PKR, although it binds to the protein and thereby prevents its activation by authentic dsRNA. In contrast, we observed that VAI RNA can both bind and activate 2-5(A) synthetase. Mutations in VAI RNA, which removed occasional mismatches present in its double-stranded stems, markedly enhanced its 2-5(A) synthetase-activating capacity. These mutants, however, are incapable of activating PKR. Other mutations, which disrupted the structure of the central stem-loop region of the VAI RNA, reduced its ability to activate 2-5(A) synthetase. These debilitated mutants could bind to the synthetase protein, although they fail to bind to PKR.

Original languageEnglish (US)
Pages (from-to)3454-3461
Number of pages8
JournalJournal of Biological Chemistry
Volume270
Issue number7
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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