Thyroid hormone receptor-associated protein 3 (THRAP3) (THRAP3)

Thyroid hormone receptor-associated protein 3 (THRAP3), also known as TRAP150, is a nuclear protein that plays a dual role in transcriptional coactivation and pre-mRNA splicing. It is a component of the thyroid hormone receptor-associated protein (TRAP) complex and the transcription-export (TREX) complex, facilitating the link between gene transcription and mRNA processing (UniProt Q9Y2W1). THRAP3 has gained significant attention as a therapeutic target due to its role in metabolic homeostasis, where it regulates the activity of Peroxisome Proliferator-Activated Receptor gamma (PPARγ) by controlling its phosphorylation (Choi et al., Nature 2014). High levels of THRAP3 are associated with insulin resistance and obesity-related inflammation, as it promotes the expression of pro-inflammatory genes while suppressing insulin-sensitizing adipokines. Consequently, targeting Thrap3 mRNA with antisense oligonucleotides (ASOs) has emerged as a strategy to treat type 2 diabetes and nonalcoholic steatohepatitis (NASH) by restoring metabolic balance (Ionis Pharmaceuticals). Preclinical studies have demonstrated that THRAP3 knockdown improves glucose tolerance and reduces hepatic steatosis without the side effects typically associated with direct PPARγ agonists. Beyond metabolism, THRAP3 is involved in the DNA damage response and the regulation of circadian rhythms, suggesting a broad impact on cellular physiology (Wakabayashi et al., Scientific Reports 2020).

Other names

TRAP150Thyroid hormone receptor-associated protein complex 150 kDa componentBCL2L11-binding protein

Antisense oligonucleotide-mediated knockdown of mRNA via RNase H1 cleavage, leading to reduced protein expression and modulation of PPAR-gamma activity.