AbstractThe non-enzymatic replication of the primordial genetic material is thought to have enabled the evolution of the first ribozymes, leading to early forms of RNA-based life. However, the reported rate of chemical RNA ligation is extremely slow. Here we show that the rate of ligation can be greatly enhanced by employing a 3′-amino group at the 3′-end of each oligonucleotide, in combination with an N-alkyl imidazole organocatalyst. These modifications allow the rapid copying of long RNA templates by multi-step ligation of tetranucleotides, as well as the assembly of long oligonucleotides from short template splints. Our work shows that a functional RNA ligase ribozyme can be assembled from relatively short oligonucleotides, demonstrating a transition from non-enzymatic ligation to enzymatic ligation. We suggest that the genomes of primitive protocells could have consisted of relatively easily replicated oligonucleotides as short as 10 to 12 nucleotides in length.
Template‐Directed Copying of RNA by Non‐enzymatic Ligation
