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Overview

The is a catalytic RNA that is capable of self cleaving. There are two groups that ribozymes may fall into based on function: splicing ribozymes and cleaving ribozymes; the latter may be further broken down into trans-cleaving nucleases and small self-cleaving ribozymes or nucleolytic ribozymes.^[1] Twister ribozyme is a member of the nucleolytic ribozymes along with 8 other classes which include hairpin, hammerhead, hatchet, hepatitis delta virus (HDV), glucosamine-6-phosphate synthase, neurospora, pistol, and twister sister. ^[1]

History

Twister ribozyme was discovered in 2013 through the use of bioinformatics. They found that the twister motif occurred in many eukaryotic and bacterial species and that it likely had various biological roles.^[2] It was believed that twister RNA represented an unknown class of self-cleaving ribozymes due to the observation that twister and hammerhead ribozymes shared similar genetic contents.^[2] This hypothesis was tested through multiple experiments proving it to be self-cleaving. The was given the name twister as the people who discovered it found it to resemble the Egyptian hieroglyph "twisted flax".

Function

The twister ribozyme displays nucleolytic ribozyme activity both in vitro and in vivo and has one of the fastest catalytic rates of naturally occurring ribozymes with similar function.^[3][4] The twister ribozyme appears to follow a SN2 mechanism for phosphodiester cleavage producing a 2',3'-cyclic phosphate and 5' hydroxyl product.^[3] Twister ribozyme produces catalytic activity by orienting the P O bond that is to be cleaved for nucleophilic attack in the active site.^[1] The ribozyme follows general acid-base catalysis which has been supported through experimental and modeling evidence.^[3] The reaction rate is dependent on temperature and pH as well as Mg2+ ions but they are not essential to the overall reaction.^[3]

Structural highlights

The structure of twister ribozyme has a highly conserved secondary structure that includes a double pseudo knot with a core comprising of a stem loop interrupted by two internal loops.^[3] The cleavage site for the ribozyme is located within loop 1 and the can be found at the center of the molecule.^[3] Active site formation of all nucleolytic ribozymes occurs through the interactions of secondary and tertiary structures.^[1] The double pseudo knot structure is formed by two long range tertiary interactions which are necessary for its catalytic function.^[1] The structure contains four magnesium ions within the ribozyme fold which are important to the stabilization of secondary structure; two have shells of water molecules and the other two have phosphate non-bridging oxygen atoms.^[3]