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Regioselective formation of RNA strands in the absence of magnesium ions

The oligomerization of ribonucleotides can produce short RNA strands in the absence of enzymes. This reaction gives one of two regioisomeric phosphodiester linkages, a 2′,5′- or a 3′,5′-diester. The former, non-natural linkage is detrimental for duplex stability, and is known to form preferentially...

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Autores principales: Motsch, Sebastian, Tremmel, Peter, Richert, Clemens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026634/
https://www.ncbi.nlm.nih.gov/pubmed/31819977
http://dx.doi.org/10.1093/nar/gkz1125
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author Motsch, Sebastian
Tremmel, Peter
Richert, Clemens
author_facet Motsch, Sebastian
Tremmel, Peter
Richert, Clemens
author_sort Motsch, Sebastian
collection PubMed
description The oligomerization of ribonucleotides can produce short RNA strands in the absence of enzymes. This reaction gives one of two regioisomeric phosphodiester linkages, a 2′,5′- or a 3′,5′-diester. The former, non-natural linkage is detrimental for duplex stability, and is known to form preferentially in oligomerizations occurring in homogeneous solution with preactivated nucleotides in the presence of magnesium cations. We have studied ribonucleotide oligomerization with in situ activation, using NMR as monitoring technique. Unexpectedly, the known preference for 2′,5′-linkages in the oligomerization of AMP was reversed in the absence of magnesium ions at slightly basic pH. Further, oligomerization was surprisingly efficient in the absence of Mg(2+) salts, producing oligomers long enough for duplex formation. A quantitative systems chemistry analysis then revealed that the absence of magnesium ions favors the activation of nucleotides, and that the high concentration of active species can compensate for slower coupling. Further, organocatalytic intermediates can help to overcome the unfavorable regioselectivity of the magnesium-catalyzed reactions. Our findings allay concerns that RNA may have been difficult to form in the absence of enzymes. They also show that there is an efficient path to genetic material that does not require mineral surfaces or cations known to catalyze RNA hydrolysis.
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spelling pubmed-70266342020-02-25 Regioselective formation of RNA strands in the absence of magnesium ions Motsch, Sebastian Tremmel, Peter Richert, Clemens Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry The oligomerization of ribonucleotides can produce short RNA strands in the absence of enzymes. This reaction gives one of two regioisomeric phosphodiester linkages, a 2′,5′- or a 3′,5′-diester. The former, non-natural linkage is detrimental for duplex stability, and is known to form preferentially in oligomerizations occurring in homogeneous solution with preactivated nucleotides in the presence of magnesium cations. We have studied ribonucleotide oligomerization with in situ activation, using NMR as monitoring technique. Unexpectedly, the known preference for 2′,5′-linkages in the oligomerization of AMP was reversed in the absence of magnesium ions at slightly basic pH. Further, oligomerization was surprisingly efficient in the absence of Mg(2+) salts, producing oligomers long enough for duplex formation. A quantitative systems chemistry analysis then revealed that the absence of magnesium ions favors the activation of nucleotides, and that the high concentration of active species can compensate for slower coupling. Further, organocatalytic intermediates can help to overcome the unfavorable regioselectivity of the magnesium-catalyzed reactions. Our findings allay concerns that RNA may have been difficult to form in the absence of enzymes. They also show that there is an efficient path to genetic material that does not require mineral surfaces or cations known to catalyze RNA hydrolysis. Oxford University Press 2020-02-20 2019-12-10 /pmc/articles/PMC7026634/ /pubmed/31819977 http://dx.doi.org/10.1093/nar/gkz1125 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Chemical Biology and Nucleic Acid Chemistry
Motsch, Sebastian
Tremmel, Peter
Richert, Clemens
Regioselective formation of RNA strands in the absence of magnesium ions
title Regioselective formation of RNA strands in the absence of magnesium ions
title_full Regioselective formation of RNA strands in the absence of magnesium ions
title_fullStr Regioselective formation of RNA strands in the absence of magnesium ions
title_full_unstemmed Regioselective formation of RNA strands in the absence of magnesium ions
title_short Regioselective formation of RNA strands in the absence of magnesium ions
title_sort regioselective formation of rna strands in the absence of magnesium ions
topic Chemical Biology and Nucleic Acid Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026634/
https://www.ncbi.nlm.nih.gov/pubmed/31819977
http://dx.doi.org/10.1093/nar/gkz1125
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