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Fundamental studies of functional nucleic acids: aptamers, riboswitches, ribozymes and DNAzymes

Please always quote using this URN: urn:nbn:de:bvb:20-opus-212133
  • This review aims at juxtaposing common versus distinct structural and functional strategies that are applied by aptamers, riboswitches, and ribozymes/DNAzymes. Focusing on recently discovered systems, we begin our analysis with small-molecule binding aptamers, with emphasis on in vitro-selected fluorogenic RNA aptamers and their different modes of ligand binding and fluorescence activation. Fundamental insights are much needed to advance RNA imaging probes for detection of exo- and endogenous RNA and for RNA process tracking. Secondly, weThis review aims at juxtaposing common versus distinct structural and functional strategies that are applied by aptamers, riboswitches, and ribozymes/DNAzymes. Focusing on recently discovered systems, we begin our analysis with small-molecule binding aptamers, with emphasis on in vitro-selected fluorogenic RNA aptamers and their different modes of ligand binding and fluorescence activation. Fundamental insights are much needed to advance RNA imaging probes for detection of exo- and endogenous RNA and for RNA process tracking. Secondly, we discuss the latest gene expression–regulating mRNA riboswitches that respond to the alarmone ppGpp, to PRPP, to NAD+, to adenosine and cytidine diphosphates, and to precursors of thiamine biosynthesis (HMP-PP), and we outline new subclasses of SAM and tetrahydrofolate-binding RNA regulators. Many riboswitches bind protein enzyme cofactors that, in principle, can catalyse a chemical reaction. For RNA, however, only one system (glmS ribozyme) has been identified in Nature thus far that utilizes a small molecule – glucosamine-6-phosphate – to participate directly in reaction catalysis (phosphodiester cleavage). We wonder why that is the case and what is to be done to reveal such likely existing cellular activities that could be more diverse than currently imagined. Thirdly, this brings us to the four latest small nucleolytic ribozymes termed twister, twister-sister, pistol, and hatchet as well as to in vitro selected DNA and RNA enzymes that promote new chemistry, mainly by exploiting their ability for RNA labelling and nucleoside modification recognition. Enormous progress in understanding the strategies of nucleic acids catalysts has been made by providing thorough structural fundaments (e.g. first structure of a DNAzyme, structures of ribozyme transition state mimics) in combination with functional assays and atomic mutagenesis.show moreshow less

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Author: Micura Ronald, Claudia HöbartnerORCiD
URN:urn:nbn:de:bvb:20-opus-212133
Document Type:Journal article
Faculties:Fakultät für Chemie und Pharmazie / Institut für Organische Chemie
Language:English
Parent Title (English):Chemical Society Reviews
Year of Completion:2020
Edition:Advance Article
Source:Chemical Society Reviews, 2020, Advance Article. DOI: 10.1039/D0CS00617C
DOI:https://doi.org/10.1039/D0CS00617C
Sonstige beteiligte Institutionen:Institute of Organic Chemistry and Center for Molecular Biosciences Innsbruck, CMBI, Leopold-Franzens University Innsbruck, Austria
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 547 Organische Chemie
Tag:Functional nucleic acids; RNA Enzymes; RNA labeling; nucleoside modification recognition
Release Date:2020/09/28
EU-Project number / Contract (GA) number:682586
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung