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Activation of Innate Immune Signaling by Viral RNAs
Author(s) -
Gehrke Lee,
Uzri Dina
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.653.1
Subject(s) - rig i , innate immune system , rna , biology , microbiology and biotechnology , interferon , pattern recognition receptor , signal transduction , biochemistry , virology , receptor , gene
RIG‐I is a host pattern recognition receptor (PRR) that is critical for innate immune signaling during RNA virus infections. RIG‐I binds to pathogen associated molecular pattern (PAMP) RNAs by recognizing the 5’ triphosphate present on uncapped viral RNAs in addition to a polyU/UC domain that is present in the hepatitis C virus (HCV) RNA 3’ untranslated region. Following RNA recognition, RIG‐I is ubiquitinylated and binds to IPS‐1, a protein localized to the outer mitochondrial membrane. The RIG‐I/IPS‐1 interaction then activates a signal transduction cascade leading to interferon expression, thus initiating an antiviral state. Our research is aimed at understanding the RNA nucleotide sequence and structural determinants for RIG‐I binding and activation. Poly U/UC RNAs containing 2’‐fluoro‐ deoxyuridine or pseudouridine substituted for uridine bind the RIG‐I protein; however, these RNAs do not activate downstream interferon expression. Short homopolymeric U or A RNAs (50 nucleotides in length) are not activators of RIG‐I signaling; however, insertion of a single C or G nucleotide, respectively, increases the RNA activation potential. These data suggest that RNAs containing interrupted U or A homopolymer sequences are targets for RIG‐I binding. Current experiments focus on using the modified RNAs to define the mechanism of RIG‐I activation that leads to innate immune signaling.