Self-replicating RNA enzyme. (a) Sequence and secondary structure of the enzyme (E), which catalyzes ligation of two substrates (A and B) to form a new copy of E. Curved arrow indicates the site of ligation. Mutations in the improved compared to original form of the enzyme are numbered and highlighted by black circles. These six mutations are: G10→U, C11→A, G14→A, A15→C, G33→C, and A38→G. (b) Self-replication cycle involving binding of A and B to E, ligation of A and B to form of a new copy of E, and dissociation of the E•E complex.