The search for a PKR code—differential regulation of protein kinase R activity by diverse RNA and protein regulators
| Autor: | Charles Bou-Nader, Jinwei Zhang, Frances E. Henderson, Jackson M. Gordon |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
RNA
Untranslated viruses Review Biology Virus Replication Protein Structure Secondary eIF-2 Kinase 03 medical and health sciences Allosteric Regulation Sense (molecular biology) Animals Humans Integrated stress response Protein Interaction Domains and Motifs Kinase activity Molecular Biology RNA Double-Stranded 030304 developmental biology 0303 health sciences Binding Sites Base Sequence Effector 030302 biochemistry & molecular biology RNA biochemical phenomena metabolism and nutrition Non-coding RNA Protein kinase R Immunity Innate Cell biology RNA silencing Gene Expression Regulation Virus Diseases Host-Pathogen Interactions Interferons Protein Binding |
| Zdroj: | RNA. 25:539-556 |
| ISSN: | 1469-9001 1355-8382 |
| DOI: | 10.1261/rna.070169.118 |
| Popis: | The interferon-inducible protein kinase R (PKR) is a key component of host innate immunity that restricts viral replication and propagation. As one of the four eIF2α kinases that sense diverse stresses and direct the integrated stress response (ISR) crucial for cell survival and proliferation, PKR's versatile roles extend well beyond antiviral defense. Targeted by numerous host and viral regulators made of RNA and proteins, PKR is subject to multiple layers of endogenous control and external manipulation, driving its rapid evolution. These versatile regulators include not only the canonical double-stranded RNA (dsRNA) that activates the kinase activity of PKR, but also highly structured viral, host, and artificial RNAs that exert a full spectrum of effects. In this review, we discuss our deepening understanding of the allosteric mechanism that connects the regulatory and effector domains of PKR, with an emphasis on diverse structured RNA regulators in comparison to their protein counterparts. Through this analysis, we conclude that much of the mechanistic details that underlie this RNA-regulated kinase await structural and functional elucidation, upon which we can then describe a “PKR code,” a set of structural and chemical features of RNA that are both descriptive and predictive for their effects on PKR. |
| Databáze: | OpenAIRE |
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