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Cell. 2014 Feb 13;156(4):800-11. doi: 10.1016/j.cell.2014.01.021.

A bicistronic MAVS transcript highlights a class of truncated variants in antiviral immunity.

Author information

1
Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
2
Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
3
Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA.
4
Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address: jonathan.kagan@childrens.harvard.edu.

Abstract

Bacterial and viral mRNAs are often polycistronic. Akin to alternative splicing, alternative translation of polycistronic messages is a mechanism to generate protein diversity and regulate gene function. Although a few examples exist, the use of polycistronic messages in mammalian cells is not widely appreciated. Here we report an example of alternative translation as a means of regulating innate immune signaling. MAVS, a regulator of antiviral innate immunity, is expressed from a bicistronic mRNA encoding a second protein, miniMAVS. This truncated variant interferes with interferon production induced by full-length MAVS, whereas both proteins positively regulate cell death. To identify other polycistronic messages, we carried out genome-wide ribosomal profiling and identified a class of antiviral truncated variants. This study therefore reveals the existence of a functionally important bicistronic antiviral mRNA and suggests a widespread role for polycistronic mRNAs in the innate immune system.

PMID:
24529381
PMCID:
PMC3959641
DOI:
10.1016/j.cell.2014.01.021
[Indexed for MEDLINE]
Free PMC Article

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