Transthyretin messenger RNA 3' untranslated region (TTR mRNA 3'UTR) (TTR mRNA 3'UTR)

The transthyretin (TTR) messenger RNA 3' untranslated region (3'UTR) is a non-coding segment of the TTR mRNA that plays a vital role in the regulation of TTR protein expression and serves as a validated therapeutic target (Adams et al., 2018, NEJM). Transthyretin is a liver-derived protein responsible for transporting thyroxine and vitamin A (via retinol-binding protein) in the blood (UniProt P02766). In patients with transthyretin-mediated amyloidosis (ATTR), the TTR protein destabilizes and forms amyloid deposits in various tissues, particularly the peripheral nerves and the heart (Benson et al., 2018, NEJM). Therapeutic agents such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) are designed to bind specifically to conserved sequences within the 3'UTR (Habtemariam et al., 2023, Clinical Pharmacokinetics). Binding of siRNAs like Patisiran and Vutrisiran leads to RISC-mediated cleavage, while ASOs like Inotersen and Eplontersen induce RNase H-mediated degradation of the mRNA (Coelho et al., 2023, JAMA). This targeted degradation results in a significant reduction in serum TTR protein levels, thereby inhibiting the formation of new amyloid fibrils and slowing the progression of the disease.

Other names

TTR mRNA 3'UTRTransthyretin 3' untranslated regionPrealbumin mRNA 3'UTRTransthyretin mRNA

RNA interference (RNAi) and RNase H-mediated mRNA degradation