RIBOZYMES: CHARACTERISTICS AND TYPES - BIOLOGY - 2024

The ribozymes are RNA (ribonucleic acid) with catalytic capacity, it is capable of accelerating the chemical reactions occurring in the body. Some ribozymes can act alone, while others require the presence of a protein to effectively catalyze.

The ribozymes discovered so far participate in reactions of generation of transfer RNA molecules and in splicing reactions: transesterification that participate in the removal of introns from RNA molecules, whether messenger, transfer or ribosomal. Depending on their function, they are classified into five groups.

Source: By Frédéric Dardel, from Wikimedia Commons

The discovery of ribozymes has piqued the interest of many biologists. These catalytic RNAs have been proposed as a potential candidate for the molecules that possibly gave rise to the first life forms.

Furthermore, like many viruses they use RNA as genetic material and many of them are catalytic. Therefore, ribozymes offer opportunities for the creation of drugs that seek to attack these catalysts.

Historical perspective

For many years it was believed that the only molecules capable of participating in biological catalysis were proteins.

Proteins are made up of twenty amino acids - each with different physical and chemical properties - that allow them to cluster into a wide variety of complex structures, such as alpha helices and beta sheets.

In 1981, the discovery of the first ribozyme occurred, ending the paradigm that the only biological molecules capable of catalyzing are proteins.

The structures of enzymes allow to take a substrate and transform it into a certain product. RNA molecules also have this ability to fold and catalyze reactions.

In fact, the structure of a ribozyme resembles that of an enzyme, with all its most prominent parts, such as the active site, the substrate binding site, and the cofactor binding site.

RNAse P was one of the first ribozymes to be discovered and consists of both proteins and RNA. It participates in the generation of transfer RNA molecules starting from larger precursors.

Characteristics of catalysis

Ribozymes are catalytic RNA molecules capable of accelerating phosphoryl group transfer reactions by orders of magnitude of 10 ⁵ to 10 ¹¹.

In laboratory experiments, they have also been shown to participate in other reactions, such as phosphate transesterification.

Types of ribozymes

There are five classes or types of ribozymes: three of these participate in self-modifying reactions, while the remaining two (ribonuclease P and ribosomal RNA) use a different substrate in the catalytic reaction. In other words, a molecule other than catalytic RNA.

Introns of group I

This type of introns has been found in mitochondrial genes of parasites, fungi, bacteria and even viruses (such as bacteriophage T4).

For example, in the protozoa of the species Tetrahymena thermofila, an intron is removed from the ribosomal RNA precursor in a series of steps: first, a nucleotide or a guanosine nucleoside reacts with the phosphodiester bond that joins the intron with the exon - reaction of transesterification.

The free exon then performs the same reaction at the exon-intron phosphodiester bond at the end of the acceptor group of the intron.

Group II introns

Group II introns are known as "self-splicing", since these RNAs are capable of self-splicing. Introns in this category are found in mitochondrial RNA precursors in the fungal lineage.

Groups I and II and ribonucleases P (see below) are ribozymes characterized by being large molecules, which can reach up to several hundred nucleotics in length, and form complex structures.

Group III introns

Group III introns are called "self-cutting" RNA and have been identified in plant pathogenic viruses.

These RNAs have the peculiarity of being able to cut themselves in the maturation reaction of genomic RNAs, starting from precursors with many units.

In this group is one of the most popular and studied ribozymes: hammerhead ribozyme. This is found in ribonucleic infectious agents of plants, called viroids.

These agents require the self-cleavage process to propagate and produce multiple copies of itself in a continuous RNA chain.

The viroids must be separated from each other, and this reaction is catalyzed by the RNA sequence found on both sides of the junction region. One of these sequences is the “hammer head” and it is named for the similarity of its secondary structure to this instrument.

Ribonuclease P

The fourth type of ribozyme is made up of both RNA and protein molecules. In ribonucleases, the structure of RNA is vital to carry out the catalytic process.

In the cellular environment, ribonuclease P acts in the same way as protein catalysts, cutting precursors of transfer RNA in order to generate a mature 5 'end.

This complex is capable of recognizing motifs whose sequences have not changed in the course of evolution (or have changed very little) of the precursors of transfer RNA. To bind the substrate with ribozyme, it does not make extensive use of complementarity between bases.

They differ from the previous group (hammerhead ribozymes) and RNAs similar to this one, by the final product of the cut: the ribonuclease produces a 5 'phosphate end.

Bacterial ribosome

Studies of the structure of the ribosome of bacteria have led to the conclusion that it also has properties of a ribozyme. The site in charge of catalysis is located in the 50S subunit.

Evolutionary implications of ribozymes

The discovery of RNAs with catalytic capacities has led to the generation of hypotheses related to the origin of life and its evolution in incipient stages.

This molecule is the basis for the "early world of RNA" hypothesis. Several authors support the hypothesis that, billions of years ago, life must have started with a certain molecule that has the ability to catalyze its own reactions.

Thus, ribozymes appear to be potential candidates for these molecules that originated the first forms of life.

References

1. Devlin, TM (2004). Biochemistry: textbook with clinical applications. I reversed.
2. Müller, S., Appel, B., Balke, D., Hieronymus, R., & Nübel, C. (2016). Thirty-five years of research into ribozymes and nucleic acid catalysis: where do we stand today ?. F1000Research, 5, F1000 Faculty Rev-1511.
3. Strobel, SA (2002). Ribozyme / Catalytic RNA. Encyclopedia of Molecular Biology.
4. Voet, D., Voet, JG, & Pratt, CW (2014). Fundamentals of Biochemistry. Panamerican Medical Ed.
5. Walter, NG, & Engelke, DR (2002). Ribozymes: catalytic RNAs that cut things, make things, and do odd and useful jobs. Biologist (London, England), 49 (5), 199.
6. Watson, JD (2006). Molecular biology of the gene. Panamerican Medical Ed.