Figure 1.

The reannealing problem and a proposed solution. a) Complete template-directed primer extension results in a full-length duplex (newly synthesized strand in maroon, original template in gray) (1). After strand separation by heating (2), subsequent cooling results in rapid reannealing of the newly synthesized complementary strand to the template strand (1); this prevents primer-template binding, outcompeting the slow process of nonenzymatic RNA polymerization (3) thereby preventing further rounds of RNA replication. b) RNA-binding oligoarginine peptides (green) inhibit strand annealing and promote further rounds of nonenzymatic replication. After an RNA duplex is formed (1), the strands are separated by heating (2). Subsequent cooling allows the peptide to bind to the separated complementary strands but not to the shorter RNA primers. This selectivity prevents reannealing of the full-length replicated strands, allowing each strand to act as a template, to which shorter primers can then bind (3). The nonenzymatic polymerization reaction is free to proceed, resulting in a complete replication cycle that would not be possible without the peptide.