RNA解旋酶ddx39a在斑马鱼胚胎发育中的功能及调控细胞增殖的分子机制研究

项目名称： RNA解旋酶ddx39a在斑马鱼胚胎发育中的功能及调控细胞增殖的分子机制研究

项目编号： No.31471354

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 娄鑫

作者单位： 南京大学

项目金额： 80万元

中文摘要： DEAD box家族RNA解旋酶是一类从古细菌到哺乳动物中高度保守的RNA解旋酶。这个家族的基因通过调节RNA的构象以及影响RNA和蛋白质之间的相互作用来调控RNA代谢的多个方面，发挥其在胚胎发育乃至癌症发生中广泛而重要的生物学功能。我们在前期工作的基础上，通过基因捕获（gene trapping）得到一个带有DEAD box家族RNA解旋酶 ddx39a功能缺失突变（null allele）的斑马鱼品系。初步的试验结果表明，ddx39a功能缺失会导致胚胎中多个器官和组织的发育缺陷以及细胞增殖的异常增多而最终导致胚胎死亡。在本项目中我们将利用斑马鱼作为模式生物，研究ddx39a在脊椎动物胚胎发育中的功能，探索ddx39a缺失发生胚胎致死的原因，阐释ddx39a在胚胎发育中调控细胞增殖分子机制。上述研究工作的突破将有助于更好地理解包括癌症等疾病的发生过程并有助于研发新的预防、诊断和治疗手段。

中文关键词： RNA解旋酶；细胞增殖；ddx39；斑马鱼；胚胎发育

英文摘要： Normal embryonic development requires a fine regulation of cell proliferation, which also the one that are deregulated during tumor formation and metastasis. Key regulators in development are also known to act as tumor suppressors or tumor-promoting factors. By understanding more about the mechanisms occurring during embryonic development, more can be understood about the molecular mechanisms underlying developmental diseases and cancer. RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism. They are associated with many processes ranging from RNA synthesis to RNA degradation. The detail function and mechanism about how these helicases engage in scenarios of animal development and diseases like cancer still remain to investigate. In previous gene trapping screen, we identified a zebrafish line carrying a null allele of ddx39a, a DEAD box RNA helicase. Preliminary data indicated the loss of ddx39a in fish embryo led to abnormalities on multiple tissues and aberrant enhanced cell proliferation. In this proposal, we planned using zebrafish embryo as model system to explore the molecular mechanisms by which ddx39a involving in development and regulating cell proliferation.

英文关键词： RNA helicase;cell proliferation;dda39;zebrafish;embryonic development