Structure, mechanism, and evolution of the mRNA capping apparatus

• Published in: Progress in Nucleic Acid Research and Molecular Biology Vol. 66; pp. 1 - 40
• Main Author: Shuman, Stewart
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Science & Technology 01.01.2001
• Subjects: Acid Anhydride Hydrolases - genetics; Acid Anhydride Hydrolases - metabolism; Animals; Biochemistry; Biophysics; Evolution, Molecular; Fungal Proteins - genetics; Fungal Proteins - metabolism; Humans; messenger RNA; Methyltransferases - genetics; Methyltransferases - metabolism; Microbiology (non-medical); mRNA (nucleoside-2'-O)-methyltransferase; Nucleotidyltransferases - genetics; Protein Binding; RNA Caps - genetics; RNA Caps - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; transferases; Vaccinia virus
• ISBN: 0125400667; 9780125400664
• ISSN: 0079-6603
• DOI: 10.1016/S0079-6603(00)66025-7

This chapter discusses the recent progress, concerning the mechanism of cap synthesis, by fungal and mammalian enzymes. Viral capping enzymes are discussed to the extent that their study illuminates the mechanistic features, shared by their cellular counterparts. The chapter discusses the structural features of the capping enzymes that are required for guanylyltransferase, triphosphatase, and methyltransferase activities. It also describes how these features are conserved in evolution. The essential structural elements illuminate the reaction mechanisms that are described briefly in this chapter. It emphasizes the importance of recent structure determinations in clarifying the mechanistic models of catalysis, opening new lines of biochemical investigation, and illuminating the surprising structural complexities for seemingly “simple” enzymatic steps. The chapter concludes with the following: (i) the cloning of genes and complementary DNA (cDNA) encoding the cap-forming enzymes from a wide variety of sources; (ii) the delineation of functional domains and catalytically essential amino acid side chains by mutagenesis; and (iii) the application of X-ray crystallography to determine the structure of the capping enzymes. The physical and functional organizations of the component activities diverged during evolution are also discussed in this chapter.