Alternative RNA Splicing

Constitutive splicing joins each exon in order to produce a single mature mRNA from a gene. Alternative RNA splicing, by contrast, uses a single gene to produce multiple types of proteins by joining different combinations of exons and introns. This allows eukaryotic cells to generate greater protein diversity than the number of genes present in their DNA.

Alternative splicing includes five types: exon skipping, the most common in humans; intron retention, more prevalent in plants; alternative 5' or 3' splice sites, which shorten or lengthen exons; and mutually exclusive exons, where only one of two exons is retained. Each type produces distinct mature mRNAs from the same pre-mRNA.

Activators bind to exonic or intronic splicing enhancers on pre-mRNA, allowing the spliceosome to recognize weak splice sites. Repressors bind to splicing silencers, preventing spliceosome assembly and causing it to skip specific splice sites. Together, these proteins tightly control which exons are included in the mature mRNA.

Cis-acting elements are DNA sequences near structural genes, primarily consisting of splicing enhancers and silencers. Trans-acting factors are molecules like SR proteins and heterogeneous nuclear ribonucleoproteins that bind to these sequences. Together, they regulate which exons are recognized and joined during splicing.

Alternative splicing allows the same gene to produce different variants of proteins in different cell types. For example, different forms of alpha tropomyosin are expressed in smooth muscle, striated muscle, and brain cells. This mechanism enables cells to generate specialized proteins suited to their specific functions without requiring separate genes.

Almost 95% of human genes are alternatively spliced, making it a widespread mechanism for protein diversity. Defects in splicing machinery can significantly impair organ function and result in diseases including cancer, neurological disorders, and heart conditions. Mutations affecting pre-mRNA splicing account for more than 15% of genetic diseases.

Yes, in some cases alternative splicing produces mature mRNA with retained introns. This intron retention type is more prevalent in plants than humans. It represents one of five distinct alternative splicing mechanisms that generate protein diversity from a single gene.