Uncovering how the spliceosome makes the cut

In eukaryotes – organisms with cells containing nuclei, from amoebae and worms to humans – the central dogma of DNA makes RNA makes protein masks a much more complex process. Messenger RNA is synthesised directly from the DNA making up the genes, but this is an immature ‘pre-mRNA’ that must undergo successive chemical modifications before it can be used in protein synthesis. It is the third and most complex of these modifications, splicing, that gives rise to the extraordinary expansion of the protein repertoire in vertebrates and, arguably, to their complex biology.

Splicing is the process through which non-coding segments of DNA, known as introns, are removed from pre-mRNA and the remaining exons joined to form one long protein-coding sequence. Almost all eukaryotes use it, but more complex organisms have gene structures that use it more frequently. Alternative splicing, in which different sets of exons from the same gene can be joined to form different proteins, occurs in about 95% of human genes. It has been suggested that the mere 20,000 or so genes in our genomes might produce as many as half a million different proteins.