Insulin-induced gene 2 messenger RNA 3' untranslated region (INSIG2 mRNA 3'-UTR)

The Insulin-induced gene 2 (INSIG2) messenger RNA 3' untranslated region (3'-UTR) is a critical regulatory segment of the INSIG2 transcript that controls the expression of the INSIG2 protein, a key negative regulator of cholesterol and fatty acid synthesis (UniProtKB Q9Y5U4). INSIG2 protein functions by sequestering the SCAP-SREBP complex within the endoplasmic reticulum, thereby preventing the proteolytic activation of SREBP transcription factors that drive lipogenic gene expression (Wikipedia). The 3'-UTR contains multiple microRNA response elements (MREs) for miRNAs such as miR-21, miR-135a, and miR-96, which bind to this region to induce mRNA degradation or translational repression (Calo et al., 2016; Aylon et al., 2016). In metabolic diseases like obesity and nonalcoholic fatty liver disease (NAFLD), these miRNAs are often upregulated, leading to suppressed INSIG2 levels and subsequent overactivation of lipid synthesis pathways (MDPI, 2024). Therapeutic strategies targeting the INSIG2 mRNA 3'-UTR include the use of antisense oligonucleotides (ASOs) to block miRNA binding or miRNA inhibitors (antagomirs) to restore INSIG2 expression and normalize lipid metabolism (Frontiers in Pharmacology, 2024). Additionally, genetic variations such as single nucleotide polymorphisms (SNPs) within or near this 3'-UTR, most notably rs7566605, have been extensively studied for their association with body mass index (BMI) and susceptibility to metabolic syndrome (Science, 2006).

Other names

INSIG2 3'-UTRInsulin-induced gene 2 3' untranslated regionINSIG2 3' untranslated regionINSIG2 mRNA 3' regulatory region

Antisense inhibition of microRNA binding, microRNA-mediated repression, RNA interference, and antisense-mediated mRNA degradation.