ARE and non-ARE Pathways Regulating CD154 mRNA Stability

调节 CD154 mRNA 稳定性的 ARE 和非 ARE 途径

• 批准号: 7274196
• 负责人: LORI Ruth COVEY
• 金额: $ 36.49万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7274196
• 关键词: CD antigens; RNA binding protein; RNA interference; T cell receptor; antigen presenting cell; autoimmunity; cell line; chemical stability; gel mobility shift assay; gene expression; genetic regulatory element; helper T lymphocyte; humoral immunity; immune response; immunofluorescence technique; leukocyte activation /transformation; mass spectrometry; messenger RNA; nucleic acid denaturation; nucleic acid metabolism; posttranslational modifications; protein purification; protein quantitation /detection; protein structure function; regulatory gene; ribonucleoproteins

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.

描述（由申请人提供）： 该计划的项目应用“ mRNA衰变在免疫系统中的作用”旨在协调研究人员的工作，特别是研究转录后调节的研究，特别是与mRNA转换有关的机制。该计划将由分子遗传学，微生物学和免疫学系主任西德尼·佩斯卡（Sidney Pestka），以及对干扰素，细胞因子，信号转导和mRNA转移的长期兴趣的研究者。该计划项目由五个项目组成：1。依从性激活的单核基因； 2。是调节CD154 mRNA稳定性的非ARE途径； 3。由TNF Alpha Au富元素进行翻译调节； 4。通过mRNA转换调节细胞因子基因表达； 5：T淋巴细胞中RANKL表达的调节。 其中四个人在研究mRNA寿命方面具有经验。两名研究人员是免疫学家。该计划项目包含一个行政核心和六个小内核，以提高工作效率有效。核心是：a）流式细胞仪设施； b）实时PCR设施； c）成像设施； d）辐照设施； e）DNA合成和测序设施； f）实时荧光共振能源设施。 该应用的总体目的是了解mRNA转换如何控制免疫反应期间免疫激活和分化的各种步骤。控制蛋白质表达变化的快速方法之一是通过修改mRNA衰变速率，这是一种转录后过程。 了解mRNA转换在免疫系统调节中的作用将为开发新的治疗剂来控制这些过程并治疗各种疾病，例如类风湿关节炎和其他免疫疾病。