Department of Chemical Biology, School of Biology and Engineering, Guizhou Medical University, Guiyang, China.
Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden.
Acta Biochim Biophys Sin (Shanghai). 2018 Jul 1;50(7):718-722. doi: 10.1093/abbs/gmy059.
G-quadruplexes are higher-order nucleic acid structures formed in G-rich sequences in DNA or RNA. G-quadruplexes are distributed in many locations in the human genome, including promoter regions, and are viewed as promising therapeutic targets. Uncoupling protein-1 (UCP1) is a mitochondrial thermogenic gene critical for energy expenditure in the form of heat in the brown adipose tissue. UCP1 is only expressed during brown fat cell differentiation and is a candidate target for treating obesity. However, the regulation of UCP1 expression is not clear. We reported here that a G-quadruplex forming sequence exists in the promoter of UCP1. The 5,10,15,20-tetra(N-methyl-4-pyridyl) porphyrin (TMPyP4) enhanced cellular expression of UCP1 and destabilized the G-quadruplex formed by the sequence from the promoter of UCP1. Mutations in the G-quadruplex regulated the cellular activity of UCP1 promoter as evidenced by a UCP1-promoter luciferase assay. These results suggest that G-quadruplex structure is a potential target to regulate the expression of UCP1.
四链体是在 DNA 或 RNA 中的富含 G 序列中形成的高级核酸结构。四链体分布在人类基因组的许多位置，包括启动子区域，被视为有前途的治疗靶点。解偶联蛋白 1（UCP1）是线粒体产热基因，对于棕色脂肪组织中以热量形式的能量消耗至关重要。UCP1 仅在棕色脂肪细胞分化过程中表达，是治疗肥胖的候选靶点。然而，UCP1 表达的调控尚不清楚。我们在这里报道，UCP1 启动子中存在一个形成四链体的序列。5,10,15,20-四（N-甲基-4-吡啶基）卟啉（TMPyP4）增强了 UCP1 的细胞表达，并使来自 UCP1 启动子的序列形成的四链体不稳定。四链体调控的突变如 UCP1-启动子荧光素酶测定所示，调节了 UCP1 启动子的细胞活性。这些结果表明，四链体结构是调节 UCP1 表达的潜在靶点。
