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Poly(U) RNA-templated synthesis of AppA

Simple nucleotide templating activities are of interest as potential primordial reactions. Here we describe the acceleration of 5′-5′ AppA synthesis by 3′-5′ poly(U) under normal solution conditions. This reaction is apparently templated via complementary U:A base-pairing, despite the involvement of...

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Autores principales: Puthenvedu, Deepa, Janas, Teresa, Majerfeld, Irene, Illangasekare, Mali, Yarus, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574757/
https://www.ncbi.nlm.nih.gov/pubmed/26272215
http://dx.doi.org/10.1261/rna.052696.115
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author Puthenvedu, Deepa
Janas, Teresa
Majerfeld, Irene
Illangasekare, Mali
Yarus, Michael
author_facet Puthenvedu, Deepa
Janas, Teresa
Majerfeld, Irene
Illangasekare, Mali
Yarus, Michael
author_sort Puthenvedu, Deepa
collection PubMed
description Simple nucleotide templating activities are of interest as potential primordial reactions. Here we describe the acceleration of 5′-5′ AppA synthesis by 3′-5′ poly(U) under normal solution conditions. This reaction is apparently templated via complementary U:A base-pairing, despite the involvement of two different RNA backbones, because poly(U), unlike other polymers, significantly stimulates AppA synthesis. These interactions occur in moderate (K(+)) and (Mg(2+)) and are temperature sensitive, being more efficient at 10°C than at 4°C, but absent at 20°C. The reaction is only slightly pH sensitive, despite potentially relevant substrate pK(a)’s. Kinetic data explicitly support production of AppA by interaction of stacked 2MeImpA and pA nucleotides paired with a single molecule of U template. At a lower rate, AppA can also be produced by a chemical reaction between 2MeImpA and pA, without participation of poly(U). Molecular modeling suggests that 5′-5′ joining between stacked or concurrently paired A's can occur without major departures from normal U-A helical coordinates. So, coenzyme-like 5′-5′ purine dinucleotides might be readily synthesized from 3′-5′ RNAs with complementary sequences.
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spelling pubmed-45747572015-10-01 Poly(U) RNA-templated synthesis of AppA Puthenvedu, Deepa Janas, Teresa Majerfeld, Irene Illangasekare, Mali Yarus, Michael RNA Article Simple nucleotide templating activities are of interest as potential primordial reactions. Here we describe the acceleration of 5′-5′ AppA synthesis by 3′-5′ poly(U) under normal solution conditions. This reaction is apparently templated via complementary U:A base-pairing, despite the involvement of two different RNA backbones, because poly(U), unlike other polymers, significantly stimulates AppA synthesis. These interactions occur in moderate (K(+)) and (Mg(2+)) and are temperature sensitive, being more efficient at 10°C than at 4°C, but absent at 20°C. The reaction is only slightly pH sensitive, despite potentially relevant substrate pK(a)’s. Kinetic data explicitly support production of AppA by interaction of stacked 2MeImpA and pA nucleotides paired with a single molecule of U template. At a lower rate, AppA can also be produced by a chemical reaction between 2MeImpA and pA, without participation of poly(U). Molecular modeling suggests that 5′-5′ joining between stacked or concurrently paired A's can occur without major departures from normal U-A helical coordinates. So, coenzyme-like 5′-5′ purine dinucleotides might be readily synthesized from 3′-5′ RNAs with complementary sequences. Cold Spring Harbor Laboratory Press 2015-10 /pmc/articles/PMC4574757/ /pubmed/26272215 http://dx.doi.org/10.1261/rna.052696.115 Text en © 2015 Puthenvedu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by/4.0/ This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Puthenvedu, Deepa
Janas, Teresa
Majerfeld, Irene
Illangasekare, Mali
Yarus, Michael
Poly(U) RNA-templated synthesis of AppA
title Poly(U) RNA-templated synthesis of AppA
title_full Poly(U) RNA-templated synthesis of AppA
title_fullStr Poly(U) RNA-templated synthesis of AppA
title_full_unstemmed Poly(U) RNA-templated synthesis of AppA
title_short Poly(U) RNA-templated synthesis of AppA
title_sort poly(u) rna-templated synthesis of appa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574757/
https://www.ncbi.nlm.nih.gov/pubmed/26272215
http://dx.doi.org/10.1261/rna.052696.115
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