低氧下miRNA对铁调节蛋白（IRPs）的调控研究

项目名称： 低氧下miRNA对铁调节蛋白（IRPs）的调控研究

项目编号： No.31300973

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 骆倩倩

作者单位： 南通大学

项目金额： 21万元

中文摘要： 铁是生命体的必需元素之一，人体拥有复杂而精密的铁调节系统。机体正常功能的发挥需要适当的氧气供给，低氧环境会导致铁调节系统中相关蛋白的变化并进一步影响铁稳态，其中包括胞内铁稳态调节者即铁调节蛋白（IRPs）。MicroRNAs（miRNAs）是在真核生物中发现的具有负调控功能的非编码RNA。miRNAs除参与细胞中的生长、代谢等基本调节途径外，在低氧应答中也扮演了重要角色。关于低氧下miRNAs对细胞铁稳态的影响报道较少。我们前期研究发现长时程低氧后IRPs蛋白显著降低，通过生物信息学预测及生物芯片初筛确定了13个低氧下IRPs的潜在特异性miRNA。本研究试图证明低氧下miRNA可参与IRPs的调控，通过确定IRPs特异性miRNA，探讨低氧下通过特定miRNA调控IRPs对胞内铁稳态的影响，为我们从基因水平调控胞内铁稳态的研究提供理论依据，该研究可能为胞内铁紊乱的诊断提供新的生物学标记。

中文关键词： 低氧；铁；铁调节蛋白；小RNA；cAMP反应元件结合蛋白

英文摘要： Iron is the essensial element in organism. Human body has a complex and rigorous iron regulatory system after a long time evolution. The concentration of oxygen plays an important role in the function of the body. Low oxygen may influence the expression of iron-related proteins involved in iron metabolism including IRPs. IRPs is also known as "the regulator of intracellular iron homeostasis".As a RNA-binding protein, IRPs regulate intracellular iron levels post-transcriptionally through binding with IREs of the target genes mRNA. MicroRNAs (miRNAs) are endogenous non-coding RNAs which are found in eukaryotes has rapidly emerged as one of the central negative regulators of expression of an extensive repertoire of genes. miRNA acts in a complex form of miRISC, then miRISC which binding of a miRNA move to its target mRNA through base-pairing mechanism with its 5' end 2 to 8 nts (termed as seed-site) complementary to recognition motif within the target mRNA. miRNAs can either inhibit translation(partial complementary) or induce degradation (full complementary) of its target mRNA, depending on the matches of the seed-site of miRNAs to its target. Recent studies have shown that miRNAs are not only involved in a variety of regulatory pathways of the body including growth and metabolism, but also play an important role

英文关键词： hypoxia；iron；IRPs；microRNA；CREB