Autocatalytic assembly of a chimeric aminoacyl-RNA synthetase ribozyme

Autocatalytic reactions driving the self-assembly of biological polymers are important for the origin of life, yet few experimental examples of such reactions exist. Here we report an autocatalytic assembly pathway that generates a chimeric, amino acid–bridged aminoacyl-RNA synthetase ribozyme. The noncovalent complex of ribozyme fragments initiates low-level aminoacylation of one of the fragments, which, after loop-closing ligation, generates a highly active covalently linked chimeric ribozyme. The generation of this ribozyme is increasingly efficient over time due to the autocatalytic assembly cycle that sustains the ribozyme over indefinite cycles of serial dilution. Because of its trans activity, this ribozyme also assembles ribozymes distinct from itself, such as the hammerhead, suggesting that RNA aminoacylation, coupled with nonenzymatic ligation, could have facilitated the emergence and propagation of ribozymes.