Functional Analysis of MicroRNAs in Lymphocyte Development and Immune Tolerance

描述（由申请人提供）：MicroRNAs （miRNAs）最近成为一类主要的反式因子，它们在mRNA水平上调节蛋白质编码基因的表达，从而控制多种生物过程，包括细胞分化、增殖和凋亡。我们和其他研究小组的遗传学研究表明，mirna参与淋巴细胞发育和功能的控制，以及自身免疫性疾病。然而，单个mirna在免疫系统中的具体功能在很大程度上仍然未知。我们建议利用新开发的慢病毒miRNA表达文库、新近发表的miRNA海绵技术和独特的B细胞耐受小鼠模型，系统评估miRNA在B细胞发育和耐受中的功能。本课题的主要目标是鉴定在B细胞发育和耐受性中发挥重要作用的mirna，从而为未来深入研究单个mirna的特定功能和分子机制开辟新的途径。

DESCRIPTION (provided by applicant): MicroRNAs (miRNAs) have recently emerged as a major class of trans-factors that regulate expression of protein coding genes at the mRNA level, thereby controlling a diverse range of biological processes including cell differentiation, proliferation, and apoptosis. Genetic studies from us and other groups have demonstrated that miRNAs are involved in the control of lymphocyte development and function, as well as in autoimmune diseases. However, the specific functions of individual miRNAs in the immune system remain largely unknown. We propose to use a newly developed lentiviral miRNA expression library, the recently published miRNA sponge technology, and a unique mouse model of B cell tolerance to systematically assess the functions of miRNAs in B cell development and tolerance. The primary goal of this proposal is to identify miRNAs that play important roles in B cell development and tolerance and, by doing so, to open up new avenues for in-depth studies of specific functions and molecular mechanisms of individual miRNAs in the future.