page_title: Ribozyme
section_title: Structure and mechanism
hierarchical_section_title: Ribozyme / Structure and mechanism
caption_attribution_description: English: Image showing the diversity of ribozyme strucutres. From Left to right: leadzyme, hammerhead ribozyme, twister ribozyme
context_page_description: Ribozymes are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonstrated that RNA can be both genetic material and a biological catalyst, and contributed to the RNA world hypothesis, which suggests that RNA may have been important in the evolution of prebiotic self-replicating systems. The most common activities of natural or in vitro-evolved ribozymes are the cleavage or ligation of RNA and DNA and peptide bond formation. Within the ribosome, ribozymes function as part of the large subunit ribosomal RNA to link amino acids during protein synthesis. They also participate in a variety of RNA processing reactions, including RNA splicing, viral replication, and transfer RNA biosynthesis. Examples of ribozymes include the hammerhead ribozyme, the VS ribozyme, Leadzyme and the hairpin ribozyme.
  Investigators studying the origin of life have produced ribozymes in the laboratory that are capable of catalyzing their own synthesis from activated monomers under very specific conditions, such as an RNA polymerase ribozyme.
context_section_description: Despite having only four choices for each monomer unit (nucleotides), compared to 20 amino acid side chains found in proteins, ribozymes have diverse structures  and mechanisms.  In many cases they are able to mimic the mechanism used by their protein counterparts.  For example, in self cleaving ribozyme RNAs, an in-line SN2 reaction is carried out using the 2’ hydroxyl group as a nucleophile attacking the bridging phosphate and causing 5’ oxygen of the N+1 base to act as a leaving group .  In comparison, RNase A, a protein that catalyzes the same reaction, uses a coordinating histidine and lysine to act as a base to attack the phosphate backbone.
  Like many protein enzymes metal binding is also critical to the function of many ribozymes. Often these interactions use both the phosphate backbone and the base of the nucleotide, causing drastic conformational changes.  There are two mechanism classes for the cleavage of phosphodiester backbone in the presence of metal. In the first mechanism, the internal 2’- OH group attacks phosphorus center in a SN₂ mechanism. Metal ions promote this reaction by first coordinating the phosphate oxygen and later stabling the oxyanion. The second mechanism also follows a SN₂ displacement, but the nucleophile comes from water or exogenous hydroxyl groups rather than RNA itself. The smallest ribozyme is UUU, which can promote the cleavage between G and A of the GAAA tetranucleotide via the first mechanism in the presence of Mn²⁺. The reason why this trinucleotide rather than the complementary tetramer catalyze this reaction may be because the UUU-AAA pairing is the weakest and most flexible trinucleotides among the 64 conformations, which provides the binding site for Mn²⁺.
  Phosphoryl transfer can also be catalyzed without metal ions. For example, pancreatic ribonuclease A and hepatitis delta virus(HDV) ribozymes can catalyze the cleavage of RNA backbone through acid-base catalysis without metal ions.  Hairpin ribozyme can also catalyze the self-cleavage of RNA without metal ions but the mechanism is still unclear.
  Ribozyme can also catalyze the formation of peptide bond between adjacent amino acid by lowering the activation entropy.
caption: Image showing the diversity of ribozyme structures.  From left to right: leadzyme, hammerhead ribozyme, twister ribozyme
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