Global Profiling of the Cellular Alternative RNA Splicing Landscape during Virus-Host Interactions.
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.
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Simon
S
Boudreault
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Camille
C
Martenon-Brodeur
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Marie
M
Caron
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Jean-Michel
JM
Garant
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Marie-Pier
MP
Tremblay
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Victoria E S
VE
Armero
Laboratoire de Génomique Fonctionnelle, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Mathieu
M
Durand
Laboratoire de Génomique Fonctionnelle, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Elvy
E
Lapointe
Laboratoire de Génomique Fonctionnelle, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Philippe
P
Thibault
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Maude
M
Tremblay-Létourneau
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Jean-Pierre
JP
Perreault
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Michelle S
MS
Scott
Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montreal, Quebec, H3C 3J7, Canada.
Guy
G
Lemay
Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec, J1E 4K8, Canada.
Martin
M
Bisaillon
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D005091:Exons; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology; D063990:Gene Ontology; D016678:Genome; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D012089:Mammalian orthoreovirus 3 / Q000254:growth & development* / Q000472:pathogenicity; D051379:Mice; D058977:Molecular Sequence Annotation; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA
D012333:RNA, Messenger