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.