What is alternative splicing and why is it important?

Alternative splicing is a process that generates multiple transcripts from a single gene. Genes, of course, store all of an organism’s genetic information and are the primary content of the genome. This process has multiple benefits, chief among them being the ability to encode a variety of proteins and phenotype traits using a single gene.

Alternative splicing, which is also known as alternative RNA splicing, is an alternative splicing process conducted during gene expression that allows one gene to code for multiple proteins. In alternative splicing, particular gene exons can be included or excluded from the final messenger RNA (mRNA) that is produced from the gene. This results in exons that are connected in different mRNA strands in unique combinations, and means that the proteins translated from alternative mRNAs will contain different amino acid sequences and a variety of biological functions.

The characteristics of an organism are determined by the information coded in DNA. A gene is part of the DNA that contains the instructions for making proteins. A closer look at a gene shows that it has two types of regions: intron and exon sequences. The information stored in a gene is transcribed from DNA into an mRNA through the process of transcription. During this process, introns are removed from the final mRNA protein transcript before they can be translated into a protein; the resulting remaining exons must then be joined through RNA splicing to produce a mature mRNA and set off the translation of a functional protein. Exons and introns can be spliced in different combinations and can give rise to different mature mRNAs from a single pre-mRNA. This process is called alternative splicing.

In 1977, two groups of scientists first described alternative splicing. Splicing in transcripts from a gene was described in 1981, and additional examples were tested through the first half of the 1980s. Subsequent discoveries focused on splicing in immunoglobin transcripts in mammals, and other tests have focused on alternative splicing in eukaryotes. More recently, in 2021, Westergren, et al. made notable findings about the adenovirus type 2 genome—in which alternative splicing was first found.

Alternative splicing means that it is possible to regulate the generation of multiple mRNA and proteins from a single gene. Stated differently, alternative splicing shows how just one gene can generate more than one mRNA transcript. Different organisms contain different numbers of introns, which can take up a large amount of the content in their DNA. Advances in next generation sequencing have made studying genome-wide alternative splicing easier, and alternative splicing has been associated with a significant percentage of human hereditary diseases, such as Parkinson’s, and cancers.