Publication Date:
2007-12-01
Description:
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-alpha). 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 immune response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nallagatla, Subba Rao -- Hwang, Jungwook -- Toroney, Rebecca -- Zheng, Xiaofeng -- Cameron, Craig E -- Bevilacqua, Philip C -- GM58709/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 30;318(5855):1455-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18048689" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Base Sequence
;
Cell Line, Tumor
;
Cercopithecus aethiops
;
DEAD-box RNA Helicases/metabolism
;
Enzyme Activation
;
Eukaryotic Initiation Factor-2/metabolism
;
Humans
;
Immunity, Innate
;
Interferon-alpha/immunology/metabolism
;
Interferon-beta/metabolism
;
Molecular Sequence Data
;
*Nucleic Acid Conformation
;
Phosphoric Monoester Hydrolases/metabolism
;
Polyphosphates/metabolism
;
RNA/chemistry/genetics/*metabolism
;
RNA, Double-Stranded/chemistry/genetics/*metabolism
;
Transfection
;
Vero Cells
;
eIF-2 Kinase/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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