Effect of single-base substitutions in the central domain of virus- associated RNA I on its function

A. Rahman, P. Malhotra, R. Dhar, T. Kewalramani, B. Thimmapaya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Adenoviruses use virus-associated RNA I (VAI RNA) to counteract the cellular antiviral response mediated by the interferon-induced, double- stranded-RNA-activated protein kinase PKR. VAI RNA is a highly structured small RNA which consists of two long duplex regions connected at the center by a complex, short stem-loop. This short stem-loop and the adjacent base- paired regions, referred to as the central domain, hind to PKR and inactivate it. Currently it is not known whether binding of VAI RNA to PKR is dependent solely on the secondary (and tertiary) structure of the central domain or whether nucleotide sequences in the central domain are also critical for this interaction. To address this question, 54 VAI mutants with single-base substitution mutations in the central domain of the RNA were constructed, and their capacities to inhibit the autophosphorylation of PKR in vitro were determined. It was found that although about half of the mutants inhibited PKR activity as efficiently as the wild type, a significant number of mutants lost the inhibitory activity substantially, without a perceptible change in their secondary structures. These results indicate that, in addition to secondary structure, at least some nucleotides in the central domain may be critical for the efficient function of VAI RNA.

Original languageEnglish (US)
Pages (from-to)4299-4307
Number of pages9
JournalJournal of virology
Volume69
Issue number7
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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