exonization

Exonization is the process by which a previously non-exonic sequence becomes part of an exon in mature mRNA. This often occurs when mutations or other genomic changes create new splice sites or enhance cryptic motifs, allowing the splicing machinery to recognize a segment that was formerly intronic or spacer DNA. In many cases, exonization involves the insertion or activation of transposable elements, such as Alu sequences, which bring along sequence features that resemble exons.

The inclusion of a new exon depends on multiple factors that govern splicing. The strength of the new splice donor and acceptor sites, the presence of branch points and polypyrimidine tracts, and the arrangement of exonic and intronic splicing enhancers and silencers all influence whether the exon is included. RNA-binding proteins and cell type–specific regulatory networks further modulate exonization, making it often tissue- or developmentally specific.

Consequences vary. Exonization can expand proteomic diversity by adding amino acids, altering reading frames, or generating regulatory motifs in untranslated regions. It can also trigger nonsense-mediated decay if a premature stop codon is introduced. Some exonizations are neutral or beneficial, contributing to gene innovation, while others may be deleterious and linked to disease. Evolutionarily, exonization provides a mechanism for new exons to arise from existing noncoding DNA, including retroelements, contributing to transcriptome complexity.

Detection of exonization relies on RNA sequencing, isoform-aware annotation, and comparative genomics, which together reveal new exons and their regulatory contexts.