title: Influenza virus mRNA trafficking through host nuclear speckles.
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.
authors: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA.
authors: Amir
authors: A
authors: Mor
authors: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA.
authors: Alexander
authors: A
authors: White
authors: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA.
authors: Ke
authors: K
authors: Zhang
authors: Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA.
authors: Matthew
authors: M
authors: Thompson
authors: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA.
authors: Matthew
authors: M
authors: Esparza
authors: Department of Microbiology, New York, New York 10029, USA.|Global Health and Emerging Pathogens Institute, New York, New York 10029, USA.
authors: Raquel
authors: R
authors: Muñoz-Moreno
authors: Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors: Kazunori
authors: K
authors: Koide
authors: Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA.
authors: Kristen W
authors: KW
authors: Lynch
authors: Department of Microbiology, New York, New York 10029, USA.|Global Health and Emerging Pathogens Institute, New York, New York 10029, USA.|Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors: Adolfo
authors: A
authors: García-Sastre
authors: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA.
authors: Beatriz M A
authors: BM
authors: Fontoura
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D002467:Cell Nucleus / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000821:virology; D012326:RNA Splicing; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D057074:Virus Release / Q000235:genetics / Q000502:physiology; D000086082:Viroporin Proteins
chemical_list: D012367:RNA, Viral; D014763:Viral Matrix Proteins; D017361:Viral Nonstructural Proteins; C085820:INS1 protein, influenza virus; C488936:M1 protein, Influenza A virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: influenza virus; mRMA export; nuclear speckles; splicing