Evolution of the substrate specificity of an RNA ligase ribozyme from phosphorimidazole to triphosphate activation.

ABSTRACT: The acquisition of new RNA functions through evolutionary processes was essential for the diversification of RNA-based primordial biology and its subsequent transition to modern biology. However, the mechanisms by which RNAs access new functions remain unclear. Do RNA enzymes need completely new folds to support new but related functions, or is reoptimization of the active site sufficient? What are the roles of neutral and adaptive mutations in evolutionary innovation? Here, we address these questions experimentally by focusing on the evolution of substrate specificity in RNA-catalyzed RNA assembly. We use directed in vitro evolution to show that a ligase ribozyme that uses prebiotically relevant 5'-phosphorimidazole-activated substrates can be evolved to catalyze ligation with substrates

SUBMITTER: DasGupta S 

PROVIDER: S-EPMC11420214 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature