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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.

SUBMITTER: Brubaker SW 

PROVIDER: S-EPMC3959641 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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

Brubaker Sky W SW   Gauthier Anna E AE   Mills Eric W EW   Ingolia Nicholas T NT   Kagan Jonathan C JC  

Cell 20140201 4


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 mR  ...[more]

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