A brilliant disguise for self RNA: 5′-End and internal modifications of primary transcripts suppress elements of innate immunity

Subba Rao Nallagatla, Rebecca Toroney, Philip C. Bevilacqua

Research output: Contribution to journalReview article

48 Scopus citations

Abstract

Interferon inducible protein kinase PKR is a component of innate immunity and mediates antiviral actions by recognizing pathogen associated molecular patterns (PAMPs). A well-known activator of PKR is long dsRNA, which can be produced during viral replication. Our recent results indicate that PKR can also be activated by short stem-loop RNA in a 5′-triphosphate-dependent fashion. A 5′-triphosphate is present primarily in foreign RNAs such as viral and bacterial transcripts, while a non-activating 5′-cap or 5′-monophosphate is present in most cellular RNAs. Additional studies indicate that internal RNA modifications and non-Watson-Crick motifs also repress PKR activation, and do so in an RNA structure-specific fashion. Interestingly, self-RNAs have more nucleoside modifications than non-self RNAs. Internal and 5′-end RNA modifications have repressive effects on other innate immune sensors as well, including TLR3, TLR7, TLR8, and RIG-I, suggesting that nucleoside modifications suppress innate immunity on a wide scale.

Original languageEnglish (US)
JournalRNA Biology
Volume5
Issue number3
DOIs
StatePublished - Jan 1 2008

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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