18.7 Alternative splicing

Introns are transcribed into complementary RNA (the primary transcript RNA). They have to be removed from the primary transcript by the spliceosome to generate the messenger RNA which is translated into protein. If there are several introns in the gene sequence, there may be several ways of removing them, and several alternative mRNAs that could be spliced together as a result.

For example, one gene in the ascomycete Verticillium dahliae (cause of wilt diseases in many plants) has been shown to use six different splice sites to produce up to five mature mRNAs. This is called alternative splicing of the primary transcripts of protein-coding genes. It is a major post-transcriptional regulatory mechanism which, in addition to regulation of transcription itself, provides the complex diversity of the transcriptome and proteome that characterises eukaryotes.

Alternative splicing is common throughout eukaryotes. Transcriptome sequencing has shown that almost 94% of human genes are alternatively spliced. In plants, estimates of alternative splicing vary from about 60% of intron-containing genes in Arabidopsis, 52% in soybean, 40% in cotton, 40% in maize, to 33% in rice.

In fungi, it has been estimated that on average, about 6 to 7% of the genes are affected by alternative splicing, but the extent of alternative splicing varies across the kingdom (and varies between species, too). In general, the number of splice variants found is lowest in the yeasts (3 in Schizosaccharomyces pombe; 9 in Saccharomyces cerevisiae), somewhat higher in filamentous ascomycetes (20 in Neurospora crassa; 100 in Aspergillus nidulans; 231 in Fusarium graminearum; 861 in Coccidioides immitis), and higher still in basidiomycetes (4819 in Schizophyllum commune).

The higher rates of alternative splicing are associated with developmental complexity and with a pathogenic lifestyle, particularly in genes involved in functions of stress response and dimorphic switching. It has been shown that alternatively spliced transcripts are regulated differentially in development.

Alternative splicing is an important regulatory mechanism, which in many eukaryotes increases the coding capacity from a limited set of genes to provide the additional complexity to the proteome that may be required for more elaborate cell functions. However, even in mammalian cells, including humans, not normally thought of as having ‘a limited set of genes’, most genes are alternatively spliced, and mutations in alternative transcripts can give rise to diseases such as cancer.

In fungi, genes involved in virulence in fungal pathogens, genes specifying transcription factors, genes involved in cell growth and morphogenesis have all been reported to be regulated by alternative splicing (Grützmann et al., 2014; Irimia & Roy, 2014; Gehrmann et al., 2016; Jin et al., 2017).

Updated July, 2018