Low-density lipoprotein receptor pre-messenger RNA (LDLR pre-mRNA) (LDLR pre-mRNA)

Low-density lipoprotein receptor (LDLR) pre-messenger RNA is the primary transcript produced from the LDLR gene, which must undergo precise splicing to generate the mature mRNA required for LDLR protein synthesis. The resulting LDLR protein is a critical cell surface receptor that facilitates the endocytosis of cholesterol-rich LDL particles from the blood, thereby maintaining systemic cholesterol homeostasis (UniProt: P01130). Mutations that disrupt the splicing of LDLR pre-mRNA are a major cause of Familial Hypercholesterolemia (FH), a genetic disorder characterized by severely elevated plasma LDL cholesterol and a high risk of premature cardiovascular disease (NCBI Gene: 3949). Therapeutic strategies targeting LDLR pre-mRNA utilize antisense oligonucleotides (ASOs) to modulate splicing patterns, such as by inducing exon skipping to bypass nonsense mutations or correcting aberrant splice site usage (PubMed: 31533900). By restoring the production of functional LDLR protein, these RNA-targeted therapies aim to lower circulating LDL-C levels in patients who are poorly served by traditional statin or PCSK9-inhibitor therapies (PubMed: 28431145). This approach represents a significant advancement in precision medicine for inherited lipid disorders.

Other names

LDLR primary transcriptLow-density lipoprotein receptor precursor mRNALDLR pre-mRNA transcript

Modulation of pre-mRNA splicing to restore the reading frame, skip mutated exons, or prevent pseudo-exon inclusion to increase functional protein expression