Role of mRNA Decay in the Immune System

描述(由申请人提供)： 本计划项目应用“信使核糖核酸在免疫系统中的作用”旨在协调一直在研究转录后调控，特别是信使核糖核酸周转机制的研究人员的努力。该项目将由Sidney Pestka指导，他是分子遗传学、微生物学和免疫学系主任，也是一名长期对干扰素、细胞因子、信号转导和信使核糖核酸周转感兴趣的研究员。该计划由五个项目组成：1.黏附激活的单核细胞基因；2.调节CD154 mRNA稳定性的ARE和Non-ARE通路；3.由肿瘤坏死因子α-AU富含元件调节翻译；4.通过mRNA周转调节细胞因子基因的表达；5：调节T淋巴细胞中RANKL的表达。 其中四人在研究信使核糖核酸寿命方面有经验；两名研究人员是免疫学家。该方案项目包括一个行政核心和六个小核心，以使工作有效率和效力。核心是：A)流式细胞仪设备；B)实时聚合酶链式反应设备；C)成像设备；D)辐射设备；E)DNA合成和测序设备；F)实时荧光共振能量设备。 这项应用的总体目标是了解在免疫反应过程中，mRNA周转是如何控制免疫激活和分化的各个步骤的。控制蛋白质表达变化的快速方法之一是通过改变mRNA衰退的速度，这是一种转录后过程。 了解信使核糖核酸在免疫系统调节中的作用，将为开发新的治疗方法来控制这些过程和治疗各种疾病提供机会，如类风湿性关节炎和其他免疫疾病。

DESCRIPTION (provided by applicant): This Program Project application "The Role of mRNA Decay in the Immune System" is designed to coordinate the efforts of investigators who have been studying post-transcriptional regulation, in particular, the mechanisms involved in mRNA turnover. The program is to be directed by Sidney Pestka, chair of the Department of Molecular Genetics, Microbiology and Immunology and an investigator with a long term interest in interferons, cytokines, signal transduction and mRNA turnover. The Program Project consists of five projects: 1. Adherence Activated Monocyte Genes; 2. ARE & non-ARE Pathways Regulating CD154 mRNA Stability; 3. Translational Regulation by the TNF Alpha AU-rich Element; 4. Regulation of Cytokine Gene Expression by mRNA Turnover; 5: Regulation of RANKL Expression in T-Lymphocytes. Four of the individuals have experience in the study of mRNA lifetime; two of the investigators are immunologists. The Program Project contains an administrative core and six small cores to make the work efficient and effective. The cores are: A) Flow Cytometry Facility; B) Real-Time PCR Facility; C) Imaging Facility; D) Irradiation Facility; E) DNA Synthesis & Sequencing Facility; F) Real time Fluorescence Resonance Energy Facility. The overall aim of this application is to understand how mRNA turnover controls various steps in immune activation and differentiation during immune responses. One of the fast methods to control changes in protein expression is by modification of the rate of mRNA decay, a post-transcriptional process. Understanding the role of mRNA turnover in regulation of the immune system will provide an opportunity to develop new therapeutics to control these processes and treat a variety of diseases such as rheumatoid arthritis and other immune disorders.