Genomic DNA splice donor and splice acceptor sequences (Splice sites) (Splice sites)

Genomic DNA splice donor and splice acceptor sequences are critical regulatory elements located at the junctions of exons and introns. The donor site (5' splice site) and acceptor site (3' splice site) contain highly conserved consensus sequences, such as the GT-AG rule, which are recognized by the U1 and U2 small nuclear ribonucleoproteins (snRNPs) of the spliceosome (Alberts et al., 2014). These sequences ensure the precise excision of introns and the ligation of exons to form mature mRNA. Mutations in these flanking sequences are a major cause of human genetic diseases, as they can lead to exon skipping, intron retention, or the creation of cryptic splice sites (Scotti & Swanson, 2016). Therapeutic strategies targeting these regions include splice-switching oligonucleotides (SSOs) and small molecules that modulate the splicing process. For example, drugs like Nusinersen and Eteplirsen bind to pre-mRNA at or near these sites to promote exon inclusion or skipping, thereby restoring functional protein production in diseases like Spinal Muscular Atrophy and Duchenne Muscular Dystrophy (Havens & Hastings, 2016). Understanding the genomic architecture of these sites is essential for developing precision medicines that correct aberrant splicing patterns. These targets represent a significant frontier in genetic medicine, moving beyond protein inhibition to direct modification of gene expression at the transcript level (Wang & Cooper, 2007).

Other names

5' splice site3' splice siteSplice donor siteSplice acceptor siteExon-intron junctionsSplice junctions

Splice modulation via steric hindrance of splicing factors or recruitment of the spliceosome to specific sites to alter exon inclusion or exclusion (Havens & Hastings, 2016).