title: A bicistronic MAVS transcript highlights a class of truncated variants in antiviral immunity.
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.
authors: Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors: Sky W
authors: SW
authors: Brubaker
authors: Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors: Anna E
authors: AE
authors: Gauthier
authors: 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.
authors: Eric W
authors: EW
authors: Mills
authors: Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA.
authors: Nicholas T
authors: NT
authors: Ingolia
authors: 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.
authors: Jonathan C
authors: JC
authors: Kagan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D016415:Sequence Alignment; D015398:Signal Transduction; D020298:U937 Cells
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human