TY - JOUR
T1 - Influenza virus mRNA trafficking through host nuclear speckles
AU - Mor, Amir
AU - White, Alexander
AU - Zhang, Ke
AU - Thompson, Matthew
AU - Esparza, Matthew
AU - Muñoz-Moreno, Raquel
AU - Koide, Kazunori
AU - Lynch, Kristen W.
AU - García-Sastre, Adolfo
AU - Fontoura, Beatriz M A
N1 - Funding Information:
was provided by National Institutes of Health (NIH) grants R01 GM113874-01, AI079110, R01 AI089539 and CPRIT RP121003-RP120718-P2 (to B.F.), NIH T32CA124334 (to A.M.), the Center for Research in Influenza Pathogenesis (CRIP) and the NIAID-funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract no. HHSN272201400008C to A.-G.S.). The authors thank R. Cadagan and K. Phelps (Live Cell Imaging Core Facility) for assistance.
Publisher Copyright:
© 2016 Macmillan Publishers Limited. All rights reserved.
PY - 2016/5/27
Y1 - 2016/5/27
N2 - 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.
AB - 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.
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U2 - 10.1038/nmicrobiol.2016.69
DO - 10.1038/nmicrobiol.2016.69
M3 - Article
C2 - 27572970
AN - SCOPUS:84988543581
SN - 2058-5276
VL - 1
JO - Nature microbiology
JF - Nature microbiology
IS - 7
M1 - 16069
ER -