Alternative Splicing
Alternative splicing is a regulated process during gene expression in which particular exons of a pre-mRNA transcript are included or excluded to generate multiple distinct mature mRNA isoforms from a single gene. This mechanism dramatically expands proteomic diversity; estimates suggest that over 95% of human multi-exon genes undergo alternative splicing, allowing a genome of ~20,000 genes to produce hundreds of thousands of protein variants. Mis-regulation of alternative splicing is implicated in many diseases including spinal muscular atrophy, various cancers, and neurological disorders.
Major Types of Alternative Splicing Events
| Type | Description | Effect on mRNA | Example Gene |
|---|---|---|---|
| Exon skipping | One or more exons are excluded | Shorter mRNA | DSCAM (Drosophila) |
| Intron retention | Intron remains in mature mRNA | Longer mRNA | Many plant genes |
| Alternative 5' splice site | Different donor site used | Altered exon boundary | SRp20 |
| Alternative 3' splice site | Different acceptor site used | Altered exon boundary | Alpha-tropomyosin |
| Mutually exclusive exons | Only one of two exons included | Two distinct proteins | Troponin T |
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Related Terms
Intron
An intron (intervening sequence) is a non-coding segment of a pre-mRNA transcript that is removed by RNA splicing before the mature mRNA is translated into protein. Introns are excised as lariat-shaped structures by the spliceosome, a large ribonucleoprotein complex that recognises conserved splice-site sequences at intron boundaries. Although historically considered "junk DNA," introns are now understood to play important roles in gene regulation, alternative splicing, and as sources of small non-coding RNAs such as snoRNAs and microRNAs.
Exon
An exon is any nucleotide sequence within a gene that is represented in the mature, spliced mRNA and is ultimately translated into protein (or retained in functional non-coding RNAs). After transcription, exons are joined together following the removal of introns to form the continuous open reading frame. The modular nature of exons provides an evolutionary advantage: exon shuffling — the rearrangement of exon modules between genes — is a major mechanism for generating new protein functions and domain architectures.
Transcription Factor
A transcription factor is a protein that binds to specific DNA sequences in the promoter or enhancer regions of a gene to control the rate of transcription by RNA polymerase. These proteins act as molecular switches, either activating or repressing gene expression in response to developmental cues, environmental signals, or cellular needs. In humans, approximately 1,600 transcription factors have been identified, and their dysregulation is linked to cancers, developmental disorders, and metabolic diseases.
From Latin "alter" (other, another) + English "splicing" (joining ends together, borrowed from sailors' rope-joining technique in the 16th century). The molecular biology usage emerged in 1977 after the discovery of introns by Sharp and Roberts.