High mobility group box 1 messenger RNA 3' untranslated region (HMGB1 mRNA 3'-UTR)

The High mobility group box 1 (HMGB1) messenger RNA 3' untranslated region (3'-UTR) is a critical regulatory sequence located at the 3' end of the HMGB1 transcript that governs the expression of the HMGB1 protein (Li et al., 2019; Ensembl). It serves as a primary site for post-transcriptional control, primarily through the binding of various microRNAs (miRNAs) such as miR-142-3p, miR-129-5p, and miR-34a, which promote mRNA degradation or inhibit translation (Li et al., 2019; Zhang et al., 2019). HMGB1 itself is a multifunctional protein that acts as a nuclear DNA chaperone and, when released extracellularly, as a potent damage-associated molecular pattern (DAMP) or alarmin that triggers inflammatory responses through receptors like RAGE and TLR4 (Yang et al., 2020; UniProt). Overexpression of HMGB1 is a hallmark of severe inflammatory conditions like sepsis, as well as various cancers and autoimmune diseases (Li et al., 2019; Frontiers in Immunology). Consequently, the HMGB1 mRNA 3'-UTR has emerged as a therapeutic target for RNA-based interventions, including miRNA mimics and antisense oligonucleotides, designed to suppress HMGB1 production (Li et al., 2019; Southwest Hospital study). Modulating this regulatory region offers a potential strategy to mitigate the damaging effects of excessive HMGB1 in diseases characterized by chronic inflammation and uncontrolled cell proliferation (Frontiers in Molecular Neuroscience). Small molecules like oxymatrine and troglitazone have also been shown to indirectly target this axis by upregulating specific miRNAs that bind to the 3'-UTR (Frontiers in Molecular Neuroscience; Southwest Hospital study). While primarily in the preclinical stage, these RNA-targeted approaches offer a specific means to modulate HMGB1 levels compared to direct protein inhibition (Expert Opinion on Therapeutic Targets).

Other names

HMG1 3'-UTRHigh mobility group protein B1 mRNA 3'-UTRHMGB1 3'-untranslated regionHMGB1 3'-UTR

miRNA-mediated mRNA degradation and translational repression