NDLI: Chemistry enters nucleic acids biology: Enzymatic mechanisms of RNA modification

Content Provider	Springer Nature Link
Author	Boschi Muller, S. Motorin, Y.
Copyright Year	2013
Abstract	Modified nucleotides are universally conserved in all living kingdoms and are present in almost all types of cellular RNAs, including tRNA, rRNA, sn(sno)RNA, and mRNA and in recently discovered regulatory RNAs. Altogether, over 110 chemically distinct RNA modifications have been characterized and localized in RNA by various analytical methods. However, this impressive list of known modified nucleotides is certainly incomplete, mainly due to difficulties in identification and characterization of these particular residues in low abundance cellular RNAs. In DNA, modified residues are formed by both enzymatic reactions (like DNA methylations, for example) and by spontaneous chemical reactions resulting from oxidative damage. In contrast, all modified residues characterized in cellular RNA molecules are formed by specific action of dedicated RNA-modification enzymes, which recognize their RNA substrate with high specificity. These RNA-modification enzymes display a great diversity in terms of the chemical reaction and use various low molecular weight cofactors (or co-substrates) in enzymatic catalysis. Depending on the nature of the target base and of the co-substrate, precise chemical mechanisms are used for appropriate activation of the base and the co-substrate in the enzyme active site. In this review, we give an extended summary of the enzymatic mechanisms involved in formation of different methylated nucleotides in RNA, as well as pseudouridine residues, which are almost universally conserved in all living organisms. Other interesting mechanisms include thiolation of uridine residues by ThiI and the reaction of guanine exchange catalyzed by TGT. The latter implies the reversible cleavage of the N-glycosidic bond in order to replace the initially encoded guanine by an aza-guanosine base. Despite the extensive studies of RNA modification and RNA-modification machinery during the last 20 years, our knowledge on the exact chemical steps involved in catalysis of RNA modification remains very limited. Recent discoveries of radical mechanisms involved in base methylation clearly demonstrate that numerous possibilities are used in Nature for these difficult reactions. Future studies are certainly required for better understanding of the enzymatic mechanisms of RNA modification, and this knowledge is crucial not only for basic research, but also for development of new therapeutic molecules.
Starting Page	1392
Ending Page	1404
Page Count	13
File Format	PDF
ISSN	00062979
Journal	Biochemistry (Moscow)
Volume Number	78
Issue Number	13
e-ISSN	16083040
Language	English
Publisher	Springer US
Publisher Date	2014-01-12
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	RNA-modification methylation pseudouridine catalytic mechanisms Biochemistry Bioorganic Chemistry Microbiology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Biochemistry Biophysics Geriatrics and Gerontology

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