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RNA Biol. 2014;11(7):875-90. doi: 10.4161/rna.29442. Epub 2014 Jun 12.

Annotation of long non-coding RNAs expressed in collaborative cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts.

Author information

1
Department of Microbiology; School of Medicine; University of Washington; Seattle, WA USA; Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA.
2
Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA; Department of Epidemiology; University of North Carolina-Chapel Hill; Chapel Hill, NC USA.
3
Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA; Department of Genetics; University of North Carolina-Chapel Hill; Chapel Hill, NC USA.
4
Department of Pathobiological Sciences; Influenza Research Institute; University of Wisconsin-Madison; Madison, WI USA.
5
Illumina, Inc.; San Diego, CA USA.
6
Department of Genetics; University of North Carolina-Chapel Hill; Chapel Hill, NC USA.

Abstract

The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions of host lncRNAs in response to influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) based on their similarity in expression with genes of known function. We performed total RNA-Seq on viral-infected lungs from eight mouse strains, yielding a large data set of transcriptional responses. Overall 5,329 lncRNAs were differentially expressed after infection. Most of the lncRNAs were co-expressed with coding genes in modules enriched in genes associated with lung homeostasis pathways or immune response processes. Each lncRNA was further individually annotated using a rank-based method, enabling us to associate 5,295 lncRNAs to at least one gene set and to predict their potential cis effects. We validated the lncRNAs predicted to be interferon-stimulated by profiling mouse responses after interferon-α treatment. Altogether, these results provide a broad categorization of potential lncRNA functions and identify subsets of lncRNAs with likely key roles in respiratory virus pathogenesis. These data are fully accessible through the MOuse NOn-Code Lung interactive database (MONOCLdb).

KEYWORDS:

collaborative cross; influenza virus; interferon; long non-coding rna; rna-seq; sars-cov

PMID:
24922324
PMCID:
PMC4179962
DOI:
10.4161/rna.29442
[Indexed for MEDLINE]
Free PMC Article

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