The RNA Exosome Syncs IAV-RNAPII Transcription to Promote Viral Ribogenesis and Infectivity

Alexander Rialdi, Judd Hultquist, David Jimenez-Morales, Zuleyma Peralta, Laura Campisi, Romain Fenouil, Natasha Moshkina, Zhen Zhen Wang, Brice Laffleur, Robyn M. Kaake, Michael J. McGregor, Kelsey Haas, Evangelos Pefanis, Randy A. Albrecht, Lars Pache, Sumit Chanda, Joanna Jen, Jordi Ochando, Minji Byun, Uttiya BasuAdolfo García-Sastre, Nevan Krogan, Harm van Bakel, Ivan Marazzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The nuclear RNA exosome is an essential multi-subunit complex that controls RNA homeostasis. Congenital mutations in RNA exosome genes are associated with neurodegenerative diseases. Little is known about the role of the RNA exosome in the cellular response to pathogens. Here, using NGS and human and mouse genetics, we show that influenza A virus (IAV) ribogenesis and growth are suppressed by impaired RNA exosome activity. Mechanistically, the nuclear RNA exosome coordinates the initial steps of viral transcription with RNAPII at host promoters. The viral polymerase complex co-opts the nuclear RNA exosome complex and cellular RNAs en route to 3′ end degradation. Exosome deficiency uncouples chromatin targeting of the viral polymerase complex and the formation of cellular:viral RNA hybrids, which are essential RNA intermediates that license transcription of antisense genomic viral RNAs. Our results suggest that evolutionary arms races have shaped the cellular RNA quality control machinery.

Original languageEnglish (US)
Pages (from-to)679-692.e14
JournalCell
Volume169
Issue number4
DOIs
StatePublished - May 4 2017

Keywords

  • Influenza virus polymerase
  • RNA chimeras
  • RNA exosome
  • RNA hybrids
  • RNA surveillance
  • RNAPII elongation
  • epigenetics
  • host-pathogen interactions
  • neurodegeneration
  • non-coding RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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