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Defining the Biology of the ADAR1-RISC Complex

定义 ADAR1-RISC 复合体的生物学

基本信息

批准号：
10879449
负责人：
Benjamin R. tenOever
金额：
$ 15.76万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10879449
关键词：
ADAR1 Antiviral Response Arthropods Biochemical Biochemistry Biogenesis Biological Biological Assay Biology C-terminal CRISPR screen Caveolae Cells Clustered Regularly Interspaced Short Palindromic Repeats Complement Complex Cytoplasm Deamination Detection Escape Mutant Eukaryotic Cell Event Excision Family Fluorescence Future Generations Immunoprecipitation Infection Integration Host Factors Interferon Type I Interferons Invertebrates Life Mammals Mediating Mediator MicroRNAs Molecular Molecular Biology Molecular Weight Pathway interactions Phosphotransferases Physiological Plants Play Positioning Attribute Process Prokaryotic Cells Protein Isoforms Proteins Proto-Oncogene Proteins c-akt RNA RNA Editing RNA Interference RNA Viruses RNA metabolism RNA-Induced Silencing Complex Recombinants Ribonuclease III Role Sendai virus Signal Transduction Site Small RNA Specificity Structure System Terminator Codon Testing Therapeutic Transcript Translations Trees Variant Vertebrates Viral Viral Proteins Virus Virus Diseases Work antagonist caveolin 1 experimental study homologous recombination invention member novel nuclease pathogen response viral RNA whole genome

项目摘要

PROJECT SUMMARY The means by which cells respond to virus infection is critical for survival. Moreover, the cellular response to virus differs dramatically depending on its position on the tree of life. This observation suggests that there are many successful strategies to inhibit virus infection, just as there are many viral antagonists that have evolved to interfere with them. Interestingly, while the cellular response to virus infection in mammals is primarily mediated by the family of Type I interferons (IFN-I), we recently characterized an IFN-I-independent defense system that involves an evolutionary conserved RNAse III nuclease. We find that this nuclease, called Drosha, rapidly translocates to the cytoplasm in response to virus infection and forms a high molecular weight structure by associating with the RNA-induced silencing complex (RISC) which we have termed the ADAR-RISC Complex or simply, ARC. Here we seek to better understand the physiological relevance of this complex.

项目总结细胞对病毒感染做出反应的方式对生存至关重要。此外，细胞对病毒根据它在生命之树上的位置而有很大的不同。这一观察结果表明，有许多成功的抑制病毒感染的策略，就像已经进化出的许多病毒拮抗剂一样去干扰他们。有趣的是，虽然哺乳动物对病毒感染的细胞反应主要是在I型干扰素家族(干扰素-I)的介导下，我们最近鉴定了一种干扰素-I非依赖性防御涉及进化保守的RNaseIII核酸酶的系统。我们发现这种名为DROSHA的核酸酶，对病毒感染迅速移位到细胞质，并形成高分子量结构通过与RNA诱导的沉默复合体(RISC)结合，我们称之为ADAR-RISC复合体或者简单地说，ARC。在这里，我们试图更好地理解这一复合体的生理相关性。