Splicesomes

In the late 1970s, it was found that eukaryotic genes are transcribed into mRNA sequences that contain conserved coding sequences (exons) and non-conserved non-coding sequences (introns). Given the notion of a chromosome as a single long length of DNA then a process of alternative splicing allows for coding sequences to be copied out from various places in a chromosome and spliced together to form different coding sequences of mRNA that generate proteins with specific characteristics. This mechanism has provided evolution with a capacity for genetic diversity, to produce families of enzymes by varying the splicing process, and a capacity to produce many more copies of functional protein than would be possible if one gene coding sequence was totally responsible for only one protein. The splicesome is a multi-component ribonucleotide protein structure that catalyses the excision of intron non-coding sequences from transcribed immature lengths of mRNA.9 Further understanding of the role and properties of the splicesome will have a great impact on genetic engineering and construction of new and novel enzymes. The enzymes in the biotechnologist’s current toolkit are those that evolution has shaped and refined to meet its needs over countless millennia. It may be that there are earlier constructs that were tried and discarded or new ones that have not yet been tested and that these can be produced using mechanisms employed by a splicesome. It is also apparent from studies on the effects of mutations that errors in the splicing process can result in
disease. A mutation responsible for mental retardation associated with lactic acidosis (Leigh’s syndrome) was found to cause binding of a human splicing regulatory factor that then caused retention rather than excision of intron sequences in the coding sequence for a subunit of the enzyme pyruvate dehydrogenase. A fuller understanding of splicesome mechanisms will help to guide therapeutic solutions for diseases caused by malfunction of splicesome activity.