Subba Rao Nallagatla,1*
Molecular patterns in pathogenic RNAs can be recognized by the
innate immune system, and a component of this response is the
interferon-induced enzyme RNA-activated protein kinase (PKR).
The major activators of PKR have been proposed to be long
double-stranded RNAs. We report that RNAs with very limited secondary
structures activate PKR in a 5''-triphosphate-dependent fashion
in vitro and in vivo. Activation of PKR by 5''-triphosphate RNA
is independent of RIG-I and is enhanced by treatment with type
1 interferon (IFN-).
Surveillance of molecular features at the 5'' end of transcripts by
PKR presents a means of allowing pathogenic RNA to be distinguished
from self-RNA. The evidence presented here suggests that this form of
RNA-based discrimination may be a critical step in mounting an early
1 Department of Chemistry, Pennsylvania State
University, University Park, PA 16802, USA.
Biosciences, Pennsylvania State University, University Park, PA 16802,
3 Department of Biochemistry and Molecular Biology, Life
Sciences College, Peking University, Beijing 100871, China.
Department of Biochemistry and Molecular Biology, Pennsylvania State University,
University Park, PA 16802, USA.
* These authors contributed equally
to this work.
correspondence should be addressed.