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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / immunology*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acid Sequence
  • Animals
  • Cell Death
  • Gene Expression Regulation*
  • Humans
  • Immunity, Innate*
  • Molecular Sequence Data
  • Protein Biosynthesis*
  • Sequence Alignment
  • Signal Transduction
  • U937 Cells


  • Adaptor Proteins, Signal Transducing
  • MAVS protein, human