SPLICING (GENETICS): WHAT IT CONSISTS OF, TYPES - BIOLOGY - 2025

The splicing or process splicing RNA, is a phenomenon that occurs in eukaryotic organisms after transcription of DNA to RNA and involves the removal of introns of a gene, retaining exons. It is considered essential in gene expression.

It occurs through events of elimination of the phosphodiester bond between exons and introns and the subsequent union of the bond between exons. Splicing occurs in all types of RNA, however it is more relevant in the messenger RNA molecule. It can also occur in DNA and protein molecules.

Source: By BCSteve, from Wikimedia Commons

It may be that when exons are assembled, they undergo an arrangement or any type of change. This event is known as alternative splicing and has important biological consequences.

What does it consist of?

A gene is a DNA sequence with the information necessary to express a phenotype. The concept of gene is not strictly restricted to DNA sequences that are expressed as proteins.

The central "dogma" of biology involves the process of transcribing DNA into an intermediate molecule, messenger RNA. This in turn is translated into proteins with the help of ribosomes.

However, in eukaryotic organisms these long gene sequences are interrupted by a type of sequence that is not necessary for the gene in question: introns. In order for the messenger RNA to be efficiently translated, these introns must be removed.

RNA splicing is a mechanism that involves various chemical reactions used to remove elements that are disrupting the sequence of a certain gene. The elements that are conserved are called exons.

Where it happens?

The spliceosome is a huge protein complex that catalyzes the splicing steps. It is made up of five types of small nuclear RNAs called U1, U2, U4, U5 and U6, as well as a series of proteins.

It is speculated that the splicing takes part in the folding of the pre-mRNA to align it correctly with the two regions where the splicing process will occur.

This complex is able to recognize the consensus sequence that most introns have near their 5 'and 3' ends. It should be noted that genes have been found in Metazoans that do not have these sequences and use another group of small nuclear RNAs for their recognition.

Types

In the literature, the term splicing is usually applied to the process that involves messenger RNA. However, there are different splicing processes that occur in other important biomolecules.

Proteins can also undergo splicing, in this case it is an amino acid sequence that is removed from the molecule.

The fragment removed is called "intein". This process occurs naturally in organisms. Molecular biology has managed to create various techniques using this principle that involve the manipulation of proteins.

Similarly, splicing also occurs at the DNA level. Thus, two DNA molecules that were previously separated are capable of being joined by means of covalent bonds.

Types of RNA splicing

On the other hand, depending on the type of RNA, there are different chemical strategies in which the gene can get rid of introns. Particularly splicing of pre-mRNA is a complicated process, since it involves a series of steps catalyzed by the spliceosome. Chemically, the process occurs by transesterification reactions.

In yeast, for example, the process begins with the cleavage of the 5 'region at the recognition site, the intron-exon "loop" is formed through a 2'-5' phosphodiester bond. The process continues with the formation of a gap in the 3 'region and finally the union of the two exons occurs.

Some of the introns that disrupt the nuclear and mitochondrial genes can be spliced ​​without the need for enzymes or energy, but rather through transesterification reactions. This phenomenon was observed in the Tetrahymena thermophila organism.

In contrast, most nuclear genes belong to the group of introns that need machinery to catalyze the removal process.

Alternative splicing

In humans it has been reported that there are about 90,000 different proteins and it was previously thought that there must be an identical number of genes.

With the arrival of new technologies and the human genome project, it was possible to conclude that we only possess about 25,000 genes. So how is it possible that we have so much protein?

The exons may not be assembled in the same order in which they were transcribed into RNA, but they may be arranged by establishing novel combinations. This phenomenon is known as alternative splicing. For this reason a single transcribed gene can produce more than one type of protein.

This incongruity between the number of proteins and the number of genes was elucidated in 1978 by the researcher Gilbert, leaving behind the traditional concept of "for a gene there is a protein."

Source: By National Human Genome Research Institute (http://www.genome.gov/Images/EdKit/bio2j_large.gif), via Wikimedia Commons

Features

For Kelemen et al. (2013) "one of the functions of this event is to increase the diversity of messenger RNAs, in addition to regulating the relationships between proteins, between proteins and nucleic acids and between proteins and membranes."

According to these authors "alternative splicing is responsible for regulating the location of proteins, their enzymatic properties and their interaction with ligands". It has also been related to the processes of cell differentiation and the development of organisms.

In the light of evolution, it appears to be an important mechanism for change, since a high proportion of higher eukaryotic organisms have been found to suffer high events of alternative splicing. In addition to playing an important role in the differentiation of species and in the evolution of the genome.

Alternative splicing and cancer

There is evidence that any error in these processes can lead to an abnormal functioning of the cell, producing serious consequences for the individual. Among these potential pathologies, cancer stands out.

For this reason, alternative splicing has been proposed as a novel biological marker for these abnormal conditions in cells. Likewise, if it is possible to fully understand the basis of the mechanism by which the disease occurs, solutions for them could be proposed.

References

1. Berg, JM, Stryer, L., & Tymoczko, JL (2007). Biochemistry. I reversed.
2. De Conti, L., Baralle, M., & Buratti, E. (2013). Exon and intron definition in pre ‐ mRNA splicing. Wiley Interdisciplinary Reviews: RNA, 4 (1), 49–60.
3. Kelemen, O., Convertini, P., Zhang, Z., Wen, Y., Shen, M., Falaleeva, M., & Stamm, S. (2013). Function of alternative splicing. Gene, 514 (1), 1–30.
4. Lamond, A. (1993). The spliceosome. Bioessays, 15 (9), 595-603.
5. Roy, B., Haupt, LM, & Griffiths, LR (2013). Review: Alternative Splicing (AS) of Genes As An Approach for Generating Protein Complexity. Current Genomics, 14 (3), 182–194.
6. Vila – Perelló, M., & Muir, TW (2010). Biological Applications of Protein Splicing. Cell, 143 (2), 191-200.
7. Liu, J., Zhang, J., Huang, B., & Wang, X. (2015). Mechanism of alternative splicing and its application in diagnosis and treatment of leukemia. Chinese Journal of Laboratory Medicine, 38 (11), 730–732.