Activation of the protein kinase PKR by short double-stranded RNAs with single-stranded tails

Xiaofeng Zheng, Philip C. Bevilacqua

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

The human RNA-activated protein kinase PKR is an interferon-induced protein that is part of the innate immune response and inhibits viral replication. The action of PKR involves RNA-dependent autophosphorylation leading to inhibition of translation. PKR has an N-terminal dsRNA-binding domain that can interact non-sequence specifically with long (>33 bp) stretches of dsRNA leading to activation. In addition, certain viral and cellular RNAs containing non-Watson-Crick structures and multiple, shorter dsRNA sections can regulate PKR. In an effort to identify novel binders and possible activators of PKR, we carried out selections on a partially structured dsRNA library using truncated and full-length versions of PKR. A library with 1011 sequences was constructed and aptamers that bound to His6-tagged proteins were isolated. Characterization revealed a novel minimal RNA motif for activation of PKR with the following unified structural characteristics: a hairpin with a nonconserved imperfect 16-bp dsRNA stem flanked by 10-15-nt single-stranded tails, herein termed a "ss-dsRNA motif." Boundary experiments revealed that the single-stranded tails flanking the dsRNA core provide the critical determinant for activation. The ss-dsRNA motif occurs in a variety of cellular and viral RNAs, suggesting possible novel functions for PKR in nature.

Original languageEnglish (US)
Pages (from-to)1934-1945
Number of pages12
JournalRNA
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2004

All Science Journal Classification (ASJC) codes

  • Molecular Biology

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