The RNA Ligase ribozyme was the first of several types of synthetic ribozymes produced by in vitro evolution and selection techniques. They are an important class of ribozymes because they catalyze the assembly of RNA fragments into phosphodiester RNA polymers, a reaction required of all extant nucleic acid polymerases and thought to be required for any self-replicating molecule. Ideas that the origin of life may have involved the first self-replicating molecules being ribozymes are called RNA World hypotheses. Ligase ribozymes may have been part of such a pre-biotic RNA world.
In order to copy RNA, fragments or monomers (individual building blocks) that have 5'-triphosphates must be ligated together. This is true for modern (protein-based) polymerases, and is also the most likely mechanism by which a ribozyme self-replicase in an RNA world might function. Yet no one has found a natural ribozyme that can perform this reaction.
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RNA in vitro evolution or SELEX enables the artificial evolution and selection of RNA molecules that possess a desired property, such as binding affinity for a particular ligand or an activity such as that of an enzyme or catalyst. The first such selections involved isolation of various aptamers that bind to small molecules. The first catalytic RNAs produced by in vitro evolution were RNA ligases, catalytic RNAs that join two RNA fragments to produce a single adduct.
RNA test tube (in vitro) evolution and selection has thus enabled several research groups to discover RNA sequences that can in fact catalyze the required chemical reaction for 5'-triphosphate RNA fragment ligation, and one group has even produced a functional RNA polymerase ribozyme.
Michael Robertson and Andrew Ellington evolved a ligase ribozyme that performs the desired 5'-3' RNA assembly reaction, and called this the L1 ligase.[1] To better understand the details of how this ribozyme folds into a structure that permits it to catalyze this fundamental reaction, the X-ray crystal structure has been solved.[2][3] The structure is composed of three helical stems called stem A, B and C, that connect at a three helix junction.