Targets and functions of the Kaposi's Sarcoma associated herpesvirus microRNAs

卡波西肉瘤相关疱疹病毒 microRNA 的靶标和功能

基本信息

批准号：
8210877
负责人：
Eva Henriette Gottwein
金额：
$ 24.15万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-05 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8210877
关键词：
3&apos Untranslated Regions Apoptosis Apoptotic Award B-Lymphocytes Binding Bioinformatics Biological Assay Biology Cell Cycle Cell Cycle Arrest Cell Cycle Progression Cell Cycle Progression Pathway Cell Cycle Regulation Cell Line Cells Collaborations Computers Data Development Ectopic Expression Endothelial Cells Faculty Functional RNA Goals Grant Herpesviridae Human Human Herpesvirus 8 Individual Induction of Apoptosis Instruction Knowledge Laboratories Lymphoma Mediating Mentorship Messenger RNA MicroRNAs Microarray Analysis Monitor Nucleotides Orthologous Gene Outcome Pathogenesis Pathway interactions Phase Physiological Porifera Positioning Attribute Property Regulation Research Research Personnel Role Shapes Technology Universities Viral Virus base effusion gammaherpesvirus interest knock-down latent infection meetings programs research study tumorigenesis tumorigenic

项目摘要

In October 2010, I am moving to an independent faculty position at Northwestern University to pursue the functional analysis of Kaposi's saroma-associated herpesvirus (KSHV) microRNAs (miRNAs). MiRNAs are -22 nucleotide long non-coding RNAs that posttranscriptionally repress mRNAs bearing imperfect matches to the miRNA, primarily in their 3'UTR. KSHV expresses a number of viral miRNAs from 12 pre-miRNAstem loops during latent infection. During the K99 phase ofthis award, I have comprehensively identified targets of all KSHV miRNAs using the newly developed PAR-CLIP technology and characterized the role of KSHV mJR-KI in the evasion of p53-mediated cell cycle arrest by KSHV. My research goal for the ROO phase of this award is to use this detailed knowledge ofthe KSHVmiRNAtargets to study the contribution ofthe KSHV miRNAs to the de-regulation of cell cycle progression and apoptosis by KSHV. Interference with these pathways by KSHV is thought to be critical for the tumorigenic properties of this virus. The interplay of the KSHV miRNAs with these pathways will be studied (a) based on PAR-CLIP-identified targets of these miRNAs with known functions in cell cycle regulation and the induction of apoptosis, (b) through systematic functional interrogation of B-cell lines or endothelial cells which ectopically express individual or multiple KSHV miRNAs, and (c) through systematic functional interrogation of latently KSHV infected primary effusion lymphoma (PEL) cells or endothelial cells in which the function of individual or multiple miRNAs has been blocked using sponges. I will monitor my development as an independent researcher through regular meetings with a newly formed mentorship committee of experts in herpesvirology miRNA biology. Furthermore, I expect that the proposed research will yield sufficient interesting data to apply for an ROI grant early in the independent phase and also significantly shape my long term research program.

2010年10月，我搬到西北大学的独立教师职位。 Kaposi与Saroma相关的疱疹病毒（KSHV）microRNA（miRNA）的功能分析。 mirnas是 -22核苷酸长的非编码RNA，转录后压抑mRNA具有不完美匹配的mRNA 对mirna，主要是在他们的3'utr中。 KSHV从12个前麦芽剂中表达许多病毒miRNA 潜在感染期间循环。在此颁奖典礼的K99阶段，我全面确定了所有KSHV miRNA都使用新开发的Par-CLIP技术，并表征了KSHV的作用 MJR-KI在KSHV逃避P53介导的细胞周期停滞中。我对ROO阶段的研究目标该奖项是利用有关KSHVMirnatargets的详细知识来研究 KSHV miRNA，通过KSHV对细胞周期进展和凋亡的凋亡进行消除。干扰这些 KSHV的途径被认为对于该病毒的致瘤特性至关重要。相互作用将研究具有这些途径的KSHV miRNA（a）基于par-clip识别的目标在细胞周期调节中具有已知功能的miRNA和凋亡的诱导，（b）通过系统 B细胞系或内皮细胞的功能询问，这些质量在异位表达个体或多个 KSHV miRNA，以及（c）通过对潜在KSHV感染的主要积液进行系统的功能询问淋巴瘤（PEL）细胞或内皮细胞，其中个体或多个miRNA的功能已是用海绵阻塞。我将通过常规监视作为独立研究人员的发展与新成立的疱疹病毒专家Mirna生物学专家指导委员会会议。此外，我希望提出的研究将产生足够的有趣数据以适用ROI 在独立阶段的早期授予，并显着塑造我的长期研究计划。