Neural precursor cell expressed developmentally down-regulated 4-like pre-mRNA exon 13 splice region (NEDD4L exon 13 splice region)

The Neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) pre-mRNA exon 13 splice region is a critical regulatory site involved in the post-transcriptional control of the NEDD4L E3 ubiquitin ligase. NEDD4L plays a pivotal role in cardiovascular health by targeting the epithelial sodium channel (ENaC) for degradation, thereby regulating sodium reabsorption in the kidneys (Araki et al., 2008). Alternative splicing at this region is significantly influenced by the rs4149601 polymorphism, where the G allele promotes the inclusion of exon 13, resulting in a protein isoform with diminished ability to ubiquitinate ENaC (Dunn et al., 2002). This leads to increased sodium retention and salt-sensitive hypertension. This specific RNA region is considered a therapeutic target for splice-switching antisense oligonucleotides (ASOs) designed to promote the skipping of exon 13. By shifting the splicing pattern toward the more active isoform, these therapies aim to restore proper ENaC regulation and provide a targeted treatment for hypertension in genetically susceptible populations (He et al., 2011).

Other names

NEDD4L exon 13rs4149601 splice siteNEDD4L alternative splice siteNEDD4L-E13

Splice-switching (exon skipping) via steric hindrance of the spliceosome at the exon 13 junction to favor the more active NEDD4L isoform.