Interferon Action and the Double‐Stranded RNA‐Dependent Enzymes ADAR1 Adenosine Deaminase and PKR Protein Kinase

• Published in: Progress in Nucleic Acid Research and Molecular Biology Vol. 81; pp. 369 - 434
• Main Authors: Toth, Ann M., Zhang, Ping, Das, Sonali, George, Cyril X., Samuel, Charles E.
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Science & Technology 2006
• Subjects: Adenosine Deaminase - chemistry; Adenosine Deaminase - genetics; Adenosine Deaminase - metabolism; Animals; Biochemistry; Communicable Diseases - enzymology; eIF-2 Kinase - genetics; eIF-2 Kinase - metabolism; Genetics (non-medical); Humans; Interferons - metabolism; Molecular biology; RNA, Double-Stranded - metabolism; RNA-Binding Proteins; ORF; hepatitis B virus; nt; vesicular stomatitis virus; base pair; nuclear localization signal; open reading frame; double‐stranded RNA‐binding domain; interferon‐stimulated response element; bp; LPS; IFN; UTR; dsRBD; NLS; adenosine deaminase acting on RNA; hepatitis C virus; single‐stranded RNA; encephalomyocarditis virus; HDV; HBV; hepatitis delta virus; dsRNA; nucleotide; nuclear export signal; untranslated region; interferon; protein kinase regulated by RNA; ADAR1; double‐stranded RNA; ssRNA; HIV; PKR; human immunodeficiency virus; kinase conserved sequence; VSV; HCV; KCS; EMCV; lipopolysaccharide; NES; ISRE
• ISBN: 9780125400817; 0125400810
• ISSN: 0079-6603
• DOI: 10.1016/S0079-6603(06)81010-X

Interferons were discovered as antiviral agents. These cytokines possess multiple activities that include the ability to affect cell growth, differentiation, and death, in addition to their hallmark ability to interfere with virus multiplication. This chapter focuses on the organization and regulated expression of the ADAR1 and PKR genes, the biochemical and biophysical properties of the ADAR1 and PKR proteins, and the mechanisms by which ADAR1 and PKR modulate the physiology of cultured cells and intact animals. Two important genes regulated by interferons are ADAR1 and PKR. ADAR1 and PKR encode double-stranded RNA (dsRNA)-binding proteins that are responsible, in part, for the biochemical and mechanistic actions of interferons. Both forms of ADAR1, p150 and p110, function to modify the expression of genetic information by changing cellular and viral RNAs through substitution of an inosine, which is recognized as guanine, for adenine. PKR is an RNA-dependent protein kinase that controls the translational pattern in cells through phosphorylation of the α subunit of protein synthesis initiation factor eIF-2; PKR also modulates signal transduction processes. The chapter discusses the roles that these proteins might play in genetic and infectious human diseases.