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

The NEDD4L pre-mRNA exon 13 splice site region is a regulatory sequence within the transcript of the Neural precursor cell expressed developmentally down-regulated protein 4-like (NEDD4L) gene (UniProt: Q96PU5). This region controls the alternative splicing of exon 13, which is pivotal in determining the functional capacity of the resulting E3 ubiquitin ligase (Dahlberg et al., 2007, Journal of Hypertension). NEDD4L plays a central role in cardiovascular health by targeting the epithelial sodium channel (ENaC) for degradation, thereby regulating sodium reabsorption in the kidneys (Araki et al., 2008, Hypertension Research). Genetic variations or splicing errors at this site, such as the rs2288774 polymorphism, are strongly associated with salt-sensitive hypertension and increased risk of stroke (PubMed: 17627187). Specifically, the exclusion of exon 13 can lead to isoforms with diminished regulatory control over ENaC, causing excessive sodium retention. As a therapeutic target, this splice site region is approached using splice-switching antisense oligonucleotides (ASOs) that redirect the splicing machinery to favor the production of active NEDD4L isoforms. This intervention facilitates the downregulation of ENaC, providing a precision medicine approach to managing hypertension in patients with specific genetic backgrounds (He et al., 2011, Journal of Biological Chemistry).

Other names

NEDD4L exon 13 splice siteNEDD4L exon 13a splice junctionNEDD4L pre-mRNA splicing regulatory elementNEDD4L rs2288774 region

Splice-switching to modulate the inclusion of exon 13, thereby increasing the expression of functional NEDD4L isoforms that downregulate the epithelial sodium channel (ENaC).