Role of mRNA Decay in the Immune System

mRNA 衰变在免疫系统中的作用

• 批准号: 7925367
• 负责人: SIDNEY PESTKA
• 金额: $ 65.59万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7925367
• 关键词: Role; mRNA; Decay; Immune; System

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）： 该计划项目应用程序“mRNA衰变在免疫系统中的作用”旨在协调研究人员的努力，他们一直在研究转录后调控，特别是mRNA周转中涉及的机制。该计划将由Sidney Pestka指导，他是分子遗传学，微生物学和免疫学系主任，也是一名对干扰素，细胞因子，信号转导和mRNA周转长期感兴趣的研究人员。该计划包括五个项目：1。粘附激活单核细胞基因; 2. ARE和非ARE途径调节CD 154 mRNA稳定性; 3.富含TNF α AU的元件的翻译调节; 4.通过mRNA更新调节细胞因子基因表达; 5：T淋巴细胞中RANKL表达的调节。 其中四人有研究mRNA寿命的经验;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核心，使工作效率和效果。核心是：A）流式细胞仪; B）实时PCR设备; C）成像设施;（D）辐照设施; E）DNA合成和测序设备; F）真实的实时荧光共振能量设备。 本申请的总体目的是了解mRNA周转如何控制免疫应答期间免疫激活和分化的各个步骤。控制蛋白质表达变化的快速方法之一是通过改变mRNA衰变的速率，这是一种转录后过程。 了解mRNA周转在免疫系统调节中的作用将为开发新的治疗方法提供机会，以控制这些过程并治疗各种疾病，如类风湿性关节炎和其他免疫疾病。

项目成果

Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation.

转化生长因子β对于 Th17 细胞分化的分子协调是不可或缺的。

• DOI: 10.1084/jem.20082286
• 发表时间: 2009-10-26
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Das, Jyoti;Ren, Guangwen;Zhang, Liying;Roberts, Arthur I.;Zhao, Xin;Bothwell, Alfred L. M.;Van Kaer, Luc;Shi, Yufang;Das, Gobardhan
• 通讯作者: Das, Gobardhan

Post-transcriptional regulation in lymphocytes: the case of CD154.

• DOI: 10.4161/rna.6.3.8581
• 发表时间: 2009-07
• 期刊: RNA biology
• 影响因子: 4.1
• 作者: Vavassori S;Covey LR
• 通讯作者: Covey LR

Nucleolin is a second component of the CD154 mRNA stability complex that regulates mRNA turnover in activated T cells.

核仁蛋白是 CD154 mRNA 稳定复合物的第二个成分，可调节活化 T 细胞中 mRNA 的周转。

• DOI: 10.4049/jimmunol.173.2.976
• 发表时间: 2004
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Singh,Karnail;Laughlin,Jennifer;Kosinski,PenelopeA;Covey,LoriR
• 通讯作者: Covey,LoriR

Polypyrimidine tract-binding protein is critical for the turnover and subcellular distribution of CD40 ligand mRNA in CD4+ T cells.

• DOI: 10.4049/jimmunol.1003236
• 发表时间: 2011-02-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Matus-Nicodemos R;Vavassori S;Castro-Faix M;Valentin-Acevedo A;Singh K;Marcelli V;Covey LR
• 通讯作者: Covey LR

Efficient co-expression of bicistronic proteins in mesenchymal stem cells by development and optimization of a multifunctional plasmid.

• DOI: 10.1186/scrt56
• 发表时间: 2011-03-14
• 期刊: Stem cell research & therapy
• 影响因子: 7.5
• 作者: Krause CD;Izotova LS;Ren G;Yuan ZR;Shi Y;Chen CC;Ron Y;Pestka S
• 通讯作者: Pestka S