Alternative splicing patterns

Alternative splicing joins different pieces of the mRNA together to make different mRNAs from the same gene. There are many ways in which this can happen to generate functionally distinct mRNAs and proteins.

Use of cassette alternative exons

The most common type of alternative splicing events (around one third) involves cassette type alternative exons. In this case an exon is either included or excluded from the mRNA. Splicing of a cassette exon can result in the complete inclusion or loss of a specific functional protein domain.

Use of alternative splice sites

In this case alternative 5’- or 3’- splice sites in exon or introns sequences are chosen leading to the inclusion or exclusion of a part of an exon or intron. The use of an alternative splice site can lead to subtle changes in the protein activity and therefore to a fine tuning of the protein function.

Intron retention

This is when an intron is not removed from the mRNA. This can lead to the incorporation of a protein sequence or a change in the reading frame.

Mutual exclusion of exons

In this splicing event, either one or other of two exons is included in the final mRNA – both mutually exclusive exons are not found together in the mRNA.

Alternative promoters and polyA sites

In addition to the above, the complexity of the mRNAs from a single gene can be increased by use of alternative promoters for transcription or polyA sites.

Different variants of alternative splicing events in higher eukaryotes

The different alternative splicing events described above can occur anywhere in the pre-mRNA.

How is everything controlled? - regulation of alternative splicing

In alternative splicing different exons of one transcript are combined in various ways. This process depends on sequences within the mRNA and on protein factors that recognise these sequences and promote or inhibit specific splicing combinations. The sequences are called splicing enhancers and silencers and can be located in exons as well as in introns. The splicing pattern depends on which factors recognised the sequences and thereby influence the selection of splice sites.

Changes in the levels of activity of these factors will change their interaction with the sequence signals and thus alter the pattern of splicing. In particular, different tissues (for example,  brain, muscle) produce proteins found only in those tissues, which alter splicing patterns of sets of genes in those tissues. So the same gene can be spliced differently in different tissues dependent on the pattern of regulatory proteins produced in these cells. The same principle is used in different developmental stages of organisms, also providing a different pattern of regulatory factors which control splicing.

Therefore, alternative splicing is controlled by a complex network of regulatory proteins and sequences on the pre-mRNA.