The overall objective of the research in The Samuel Lab is to elucidate in molecular terms the mechanisms by which interferons exert their antiviral and cell growth control actions in mammalian cells. Present work includes biochemical and molecular genetic studies of two interferon-inducible enzymes, PKR and ADAR. PKR is a double-stranded RNA-dependent protein kinase induced by IFN, and activated by RNA-dependent autophosphorylation. PKR plays a major role in the regulation of translation of viral and cellular mRNAs and also modulates transcription and signaling. The ADAR1 deaminase is an RNA editing-enzyme that catalyzes the C-6 deamination of adenosine to yield inosine, thereby altering the genetic decoding and structure of RNAs. While PKR displays antiviral and proapoptic activities, ADAR1 is often proviral and antiapoptotic in virus-infected cells. Furthermore, PKR is not required for normal mouse embryogenesis, whereas ADAR1 is required.