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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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Detalles Bibliográficos
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
Descripción
Sumario: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.