title: Regulation of innate immunity through RNA structure and the protein kinase PKR.
abstract: Molecular recognition of RNA structure is key to innate immunity. The protein kinase PKR differentiates self from non-self by recognition of molecular patterns in RNA. Certain biological RNAs induce autophosphorylation of PKR, activating it to phosphorylate eukaryotic initiation factor 2α (eIF2α), which leads to inhibition of translation. Additional biological RNAs inhibit PKR, while still others have no effect. The aim of this article is to develop a cohesive framework for understanding and predicting PKR function in the context of diverse RNA structure. We present effects of recently characterized viral and cellular RNAs on regulation of PKR, as well as siRNAs. A central conclusion is that assembly of accessible long double-stranded RNA (dsRNA) elements within biological RNAs plays a key role in regulation of PKR kinase. Strategies for forming such elements include RNA dimerization, formation of symmetrical helical defects, A-form dsRNA mimicry, and coaxial stacking of helices.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, 104 Chemistry Bldg, University Park, PA 16802, USA.
authors.forename: Subba Rao
authors.initials: SR
authors.lastname: Nallagatla
authors.forename: Rebecca
authors.initials: R
authors.lastname: Toroney
authors.forename: Philip C
authors.initials: PC
authors.lastname: Bevilacqua
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D007113:Immunity, Innate; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D012313:RNA; D019892:eIF-2 Kinase