Mechanisms of catalytic RNA molecules

Abstract

Ribozymes are folded catalytic RNA molecules that perform important biological functions. Since the discovery of the first RNA with catalytic activity in 1982, a large number of ribozymes have been reported. While most catalytic RNA molecules act alone, some RNA-based catalysts, such as RNase P, the ribosome, and the spliceosome, need protein components to perform their functions in the cell. In the last decades, the structure and mechanism of several ribozymes have been studied in detail. Aside from the ribosome, which catalyzes peptide bond formation during protein synthesis, the majority of known ribozymes carry out mostly phosphoryl transfer reactions, notably trans-esterification or hydrolysis reactions. In this review, we describe the main features of the mechanisms of various types of ribozymes that can function with or without the help of proteins to perform their biological functions.

Keywords: catalytic RNA; mechanism; ribozymes.

Figure 1.. Examples of different catalytic strategies in ribozymes.

A) Diagram illustrating the active site of the Schistosoma mansoni hammerhead ribozyme (PDB 3ZP8 (56)). The hammerhead ribozyme (grey) uses general acid base catalysis to cleave its substrate (yellow) through the involvement of a nucleobase (57). The structure contains a 2’-O-methyl to prevent cleavage (labeled O2’ in the figure). B) Diagram illustating the active site of a post-cleavage a complex of Thermotoga maritima RNase P (grey) in complex with tRNA (yellow) and 5’ leader (blue) (PDB 3Q1R (21)). The two magnesium ions are shown as green spheres.RNase P, like many other ribozymes, employs a two metal ion mechanism to cleave its target RNA. C) Diagram illustrating the peptidyltransference center (PTC) of the Haloarcula marismortui ribosome (PDB 1VQN (58)). The ribosome active site is composed solely of RNA. In the diagram, the 23S ribosomal subunit is shown in grey, cytidine-cytidine-adenosine-phenylalanine-caproic acid-biotin in the P-site is shown in gold, and cytidine-cytidine-hydroxypuromycin in the A-site is shown in blue. The α-amino group in the latter is replaced by an hydroxyl to slow down the reaction. The ribosome illustrates a ribozyme not involved in a phosphoryl transfer reaction.