Global Profiling of the Cellular Alternative RNA Splicing Landscape during Virus-Host Interactions

PLoS One. 2016 Sep 6;11(9):e0161914. doi: 10.1371/journal.pone.0161914. eCollection 2016.

Abstract

Alternative splicing (AS) is a central mechanism of genetic regulation which modifies the sequence of RNA transcripts in higher eukaryotes. AS has been shown to increase both the variability and diversity of the cellular proteome by changing the composition of resulting proteins through differential choice of exons to be included in mature mRNAs. In the present study, alterations to the global RNA splicing landscape of cellular genes upon viral infection were investigated using mammalian reovirus as a model. Our study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in eukaryotic cells following infection with a human virus. We identify 240 modified alternative splicing events upon infection which belong to transcripts frequently involved in the regulation of gene expression and RNA metabolism. Using mass spectrometry, we also confirm modifications to transcript-specific peptides resulting from AS in virus-infected cells. These findings provide additional insights into the complexity of virus-host interactions as these splice variants expand proteome diversity and function during viral infection.

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Exons
  • Fibroblasts / metabolism*
  • Fibroblasts / virology
  • Gene Ontology
  • Genome*
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Mammalian orthoreovirus 3 / growth & development*
  • Mammalian orthoreovirus 3 / pathogenicity
  • Mice
  • Molecular Sequence Annotation
  • Proteomics
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Sequence Analysis, RNA

Substances

  • RNA, Messenger

Grant support

This work was supported by grants from the Centre de recherche du Centre hospitalier universitaire de Sherbrooke (MB and JPP), the Faculté de médecine et des sciences de la santé de l’Université de Sherbrooke (MB and JPP), and the Natural Sciences and Engineering Research Council of Canada (GL). JPP holds the Université de Sherbrooke Research Chair in Structure and Genomic RNA. MB is a Chercheur-boursier Sénior from the Fonds de recherche du Québec-Santé (FRQ-S), and SB holds graduate training awards from the FRQ-S and Natural Sciences and Engineering Research Council of Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.