Two mutations in the C-terminal domain of influenza virus RNA polymerase PB2 enhance transcription by enhancing cap-1 RNA binding activity

Shijian Zhang, Qiang Wang, Jinlan Wang, Kiyohisa Mizumoto, Tetsuya Toyoda

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Influenza virus RNA polymerase (RdRp) PB2 is the cap-1 binding subunit and determines host range and pathogenicity. The mutant human influenza virus RdRp containing PB2 D701N and D701N/S714R demonstrated enhanced replicon activity in mammalian cells. We investigated the influence of these mutations on RdRp activity. Cap-1-dependent transcription activities of D701N/S714R, D701N, and S714R were 348.1 ± 6.2%, 146.4 ± 11%, and 250.1 ± 0.8% of that of the wild type (wt), respectively. Replication activity of these mutants for complimentary RNA to viral RNA ranged from 44% to 53% of that of the wt. Cap-1 RNA-binding activities of D701N/S714R, D701N, and S714R were 262 ± 25%, 257 ± 34%, and 315 ± 9.6% of that of the wt, respectively, and their cap-dependent endonuclease activities were similar to that of the wt. These mutations did not affect template RNA-binding activities. D701N and S714R mutations enhanced transcription by enhancing cap-1 RNA-binding activity, but they may exhibit decreased efficiency of priming by the cap-1 primer. These mutations at the C-terminal domain of PB2 may affect its cap-binding domain.

Original languageEnglish (US)
Pages (from-to)78-83
Number of pages6
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1819
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Cap-1 RNA binding
  • Cap-dependent nuclease
  • Influenza virus
  • PB2
  • RNA polymerase
  • Transcription

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

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