ESES

ESEs, short for exonic splicing enhancers, are cis-acting RNA elements located within coding exons of pre-mRNA. They regulate splicing by promoting the inclusion of the exon in the mature transcript, contributing to both constitutive and alternative splicing patterns.

Functionally, ESEs work by binding serine/arginine-rich (SR) splicing factors and other components of the splicing machinery. This binding helps recruit or stabilize the recognition of nearby splice sites by the spliceosome, thereby increasing the likelihood that the exon is retained in the final mRNA. ESE activity is often context-dependent, influenced by the strength of adjacent splice sites, RNA secondary structure, and transcriptional elongation rate. ESEs can interact with intronic enhancers or silencers to shape exon choice across different cell types and developmental stages.

Sequence motifs of ESEs are diverse and not uniformly conserved. They frequently exhibit purine-rich character and can occur in multiple copies within a single exon, creating combinatorial control over splicing. Evolutionarily, ESEs contribute to transcript and protein diversity by enabling modular changes in exon inclusion without altering the protein-coding frame.

Clinical and research relevance arises because mutations that disrupt ESEs can alter splicing and lead to disease, while creation of novel ESEs can cause aberrant exon inclusion. Understanding ESEs aids in predicting splicing outcomes and informs therapeutic strategies, including antisense oligonucleotides designed to modulate ESE activity. Techniques for studying ESEs include minigene assays, computational motif analyses, and protein-RNA interaction studies to map SR protein binding.