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  Functional hallmarks of a catalytic DNA that makes lariat RNA.

Javadi Zarnaghi, F., & Höbartner, C. (2016). Functional hallmarks of a catalytic DNA that makes lariat RNA. Chemistry-A European Journal, 22(11), 3720-3728. doi:10.1002/chem.201503238.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-171E-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-DB7E-C
Genre: Journal Article

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Javadi Zarnaghi, F.1, Author              
Höbartner, C.1, Author              
Affiliations:
1Research Group of Nucleic Acid Chemistry, MPI for biophysical chemistry, Max Planck Society, ou_578605              

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Free keywords: Deoxyribozymes; DNA catalysis; DNA structures; Nucleic acids; RNA
 Abstract: Catalytic DNAs, also known as deoxyribozymes, are of practical value for the synthesis of structurally or topologically complex RNAs, but little is known about the molecular details of DNA catalysis. We have investigated a deoxyribozyme that catalyzes the formation of a specific intramolecular 2′,5′-phosphodiester bond to produce lariat RNA, which is an important biological intermediate in eukaryotic mRNA splicing. The results of combinatorial mutation interference analysis (CoMA) allowed us to shrink the catalytic core to 70 % of its original length and revealed that the essential part of the deoxyribozyme sequence contained more than 50 % guanosines. Nucleotide analogue interference mapping (dNAIM) and dimethyl sulfate interference (DMSi) experiments provided atomic details of individual guanosine functional groups. Additional spectroscopic experiments and structural probing data identified conformational changes upon metal-ion binding and catalysis. Overall, this comprehensive analysis of the DNA-catalyzed reaction has provided specific insights into the synthesis of 2′,5′-branched RNA, and suggested the general features of deoxyribozymes that catalyze nucleic acid ligation reactions.

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Language(s): eng - English
 Dates: 2015-11-032016-03-07
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1002/chem.201503238
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Title: Chemistry-A European Journal
Source Genre: Journal
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Pages: - Volume / Issue: 22 (11) Sequence Number: - Start / End Page: 3720 - 3728 Identifier: -