Influenza virus mRNA trafficking through host nuclear speckles

Amir Mor, Alexander White, Ke Zhang, Matthew Thompson, Matthew Esparza, Raquel Muñoz-Moreno, Kazunori Koide, Kristen W. Lynch, Adolfo García-Sastre, Beatriz M A Fontoura

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Influenza A virus is a human pathogen with a genome composed of eight viral RNA segments that replicate in the nucleus. Two viral mRNAs are alternatively spliced. The unspliced M1 mRNA is translated into the matrix M1 protein, while the ion channel M2 protein is generated after alternative splicing. These proteins are critical mediators of viral trafficking and budding. We show that the influenza virus uses nuclear speckles to promote post-transcriptional splicing of its M1 mRNA. We assign previously unknown roles for the viral NS1 protein and cellular factors to an intranuclear trafficking pathway that targets the viral M1 mRNA to nuclear speckles, mediates splicing at these nuclear bodies and exports the spliced M2 mRNA from the nucleus. Given that nuclear speckles are storage sites for splicing factors, which leave these sites to splice cellular pre-mRNAs at transcribing genes, we reveal a functional subversion of nuclear speckles to promote viral gene expression.

Original languageEnglish (US)
Article number16069
JournalNature microbiology
Volume1
Issue number7
DOIs
StatePublished - May 27 2016

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

Cite this

Mor, A., White, A., Zhang, K., Thompson, M., Esparza, M., Muñoz-Moreno, R., Koide, K., Lynch, K. W., García-Sastre, A., & Fontoura, B. M. A. (2016). Influenza virus mRNA trafficking through host nuclear speckles. Nature microbiology, 1(7), [16069]. https://doi.org/10.1038/nmicrobiol.2016.69