What is alternative splicing?

Splicing connects

Photograph of a rope

The term 'splice' may refer to the connection of two or more pieces of any linear material. It is used in mariner’s language for connecting the endings of a rope. Tape splice means the joining of audio tape; the same is true for film material. In electrical splicing wires in electrical wiring are joined together.

In genetics the term splicing is used for the connection of two ends of parts of RNA molecule that is derived from a gene, to give the final molecule of messenger RNA that is further translated into a protein.

Splicing on Youtube

Play the splicing video on YouTube

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Splicing – the sp(l)ice of life

Every cell in our body is full of DNA, RNA and thousands of proteins and other chemicals. Different cells contain a different make-up of proteins.

Did you ever ask yourself...

How do we get protein products from genes?

The genetic information of every known organism is stored in long chains of DNA (deoxyribonucleic-acid) molecules. The functional units of the genome are genes, which are arranged in succession on the DNA strands. Usually one gene codes for one protein, meaning that the sequence of the DNA determines the sequence of amino acids forming one specific protein.

However, the information stored in the DNA cannot be translated into a protein directly; the DNA rather serves as a template which is copied into RNA (ribonucleic-acid) molecules. This process is called transcription. The product, the messenger-RNA (mRNA), is the working unit of the genome. It provides the link between the code stored in the DNA or gene and the protein product. The messenger RNA is recognised by a big cellular machine – called the ribosome – which is able to decipher the information encoded by the RNA and translates it into a sequence of amino acids that forms the protein molecule. This process is termed translation. The succession of events described is called gene expression; it is performed in the described order in every cell of every living organism known.

But now it gets a little more complicated…

Most genes are made up of pieces of DNA which code for proteins (exons) and pieces which don’t (introns). When the gene is transcribed the messenger RNA also contains exons and introns. Before the messenger RNA can be translated all of the introns must be cut out and the pieces of exons joined together (this is where ‘splice’ comes from).

In order to avoid mistakes in the final product (functional protein) the pre-mRNA must be spliced correctly. If mRNA is not pasted together properly it will result in the defective protein and might lead to disease or could even be fatal. If you want to read about link between diseases and splicing, please refer to our section Alternative Splicing and Health.

Diagram showing the gene expression pathway

The gene expression pathway

The genome or DNA is located in the cellular nucleus where it is transcribed and the pre-mRNA is formed. After several RNA processing steps (including splicing) the mature mRNA is transported to the cytoplasm where protein production proceeds (translation).

The human genome

One of the big surprises when the human genome was finally sequenced was that there were only 25,000 – 30,000 genes. We thought that as very complex animals we would have lots more genes than other animals or plants. In fact, we have the same number of genes as rice and other plants, but more than fruit flies or nematodes.

Did you ever ask yourself...

How is it possible to run all the functions of a human body with all its functions and abilities with this low number of only 25,000 – 30,000 genes?

Answer: Alternative splicing

Humans produce around 150,000 different proteins from their 25,000 – 30,000 genes. They do this by alternative splicing (AS). Alternative splicing means, that during the RNA splicing event different combinations of exons can be joined together to create a diverse array of mRNAs from a single pre-mRNA. When these are translated they produce different proteins which do different things. The production of these proteins in the right cell, in the right amount and at the right time means that alternative splicing must be highly controlled.

More than 70% of the human protein-coding genes are alternatively spliced. This explains the fact that the relatively small number of 25,000 genes can lead to over 100,000 of proteins. Alternative splicing is involved in all aspects of our growth and development and how our bodies work.

It might be surprising but alternative splicing is responsible for many basic human characteristics, for example for hearing. To find out more, please follow the link Music to our ear requires alternative splicing and Alternative view of the obesity problem.