Covalent Catalytic Strategies for Enzymes That Modify RNA Molecules on their Tripartite Building Blocks.
ACS Chem Biol
; 17(10): 2686-2703, 2022 Oct 21.
Article
in English
| MEDLINE | ID: covidwho-2028640
ABSTRACT
The tripartite structures of the four 5'-nucleotide monophosphate (NMP) building blocks in all RNAs enable enzyme-catalyzed chemical modifications to three types of sites the heterocyclic bases via N- and C-methylations and other alkylations, conversion of the N-glycoside linkages of the uridine moiety to the C-C glycoside link in pseudouridines, and the phosphodiester-mediated processes of 5'-capping, splicing, and 3'-tailing of premRNAs. We examine known cases for enzymatic covalent catalytic strategies that entail transient formation and breakdown of covalent enzyme-RNA adducts in each catalytic cycle. One case involves generation of the required carbon nucleophile during C5 methylation of cytosine residues in RNAs. A second examines the mechanism proposed for pseudouridine synthases and for replacement of a guanine residue in tRNAs by queuosine. The third category involves phosphoric anhydride and phosphodiester chemistry by which viral RNAs encode enzymes for making their own mRNA 5'-caps. This strategy includes the recent finding that the SARS-CoV2 proteins assemble a canonical 5',5'-GTP cap on their 28â¯900 nucleotide genomic RNA to enable its translation as an mRNA by host translational machinery by way of a covalent RNA-viral enzyme intermediate.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA, Viral
/
COVID-19
Limits:
Humans
Language:
English
Journal:
ACS Chem Biol
Year:
2022
Document Type:
Article
Affiliation country:
Acschembio.2c00584
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