Laboratory of Genomic Physiology and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, People's Republic of China.
Neurochem Res. 2011 Jun;36(6):1027-36. doi: 10.1007/s11064-011-0443-0. Epub 2011 Mar 22.
The candidate plasticity related gene 15 (cpg15) plays important roles in neural development and plasticity. In the present study, we studied the role of the cpg15 3'-untranslated region (UTR) in regulating the expression of the gene. The results showed that the presence of the 3'-UTR significantly decreases, while loss of a putative AU-rich element (ARE) in the 3'-UTR increases the cpg15 expression, indicating that the 3'-UTR and ARE may be essential for regulation of cpg15 expression. In addition, HuD, a neural-specific RNA binding protein, increased the cpg15 expression, which depends on the presence of the 3'-UTR and ARE. RNA-binding protein immunoprecipitation (RIP) assay demonstrated that HuD forms a complex with cpg15 mRNA in the cells of rat hippocampus. Deletion of HuD domains RRM1 plus RRM2 or Hinge region plus RRM3 attenuates the function of HuD in enhancing the cpg15 expression. The results suggest that HuD regulates the cpg15 expression via the 3'-UTR-mediated mechanism, which requires the presence of the ARE.
候选可塑性相关基因 15(cpg15)在神经发育和可塑性中发挥重要作用。在本研究中,我们研究了 cpg15 3'-非翻译区(UTR)在调节基因表达中的作用。结果表明,3'-UTR 的存在显著降低,而 3'-UTR 中假定的 AU 丰富元件(ARE)的缺失增加了 cpg15 的表达,表明 3'-UTR 和 ARE 可能是调节 cpg15 表达的必要条件。此外,神经特异性 RNA 结合蛋白 HuD 增加了 cpg15 的表达,这依赖于 3'-UTR 和 ARE 的存在。RNA 结合蛋白免疫沉淀(RIP)实验表明,HuD 在大鼠海马细胞中与 cpg15 mRNA 形成复合物。HuD 的 RRM1 加 RRM2 或铰链区加 RRM3 结构域的缺失减弱了 HuD 增强 cpg15 表达的功能。结果表明,HuD 通过 3'-UTR 介导的机制调节 cpg15 的表达,这需要 ARE 的存在。