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

Cell. 2017 May 4;169(4):679-692.e14. doi: 10.1016/j.cell.2017.04.021.


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.

Keywords: Influenza virus polymerase; RNA chimeras; RNA exosome; RNA hybrids; RNA surveillance; RNAPII elongation; epigenetics; host-pathogen interactions; neurodegeneration; non-coding RNA.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • A549 Cells
  • Animals
  • Chromatin Immunoprecipitation
  • Exoribonucleases / genetics
  • Exosome Multienzyme Ribonuclease Complex / genetics
  • Exosomes / metabolism
  • Host-Pathogen Interactions*
  • Humans
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza A Virus, H3N2 Subtype / physiology*
  • Influenza, Human / virology*
  • Mass Spectrometry
  • Mice
  • Mutation
  • Neurodegenerative Diseases / virology
  • RNA Polymerase II / metabolism*
  • RNA-Binding Proteins / genetics
  • Ribosomes / genetics
  • Transcription, Genetic


  • EXOSC3 protein, human
  • RNA-Binding Proteins
  • RNA Polymerase II
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex
  • EXOSC10 protein, human