Defining the Biology of the ADAR1-RISC Complex

定义 ADAR1-RISC 复合体的生物学

• 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
• 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

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.

项目概要 细胞对病毒感染的反应方式对于生存至关重要。此外，细胞对 病毒根据其在生命树上的位置而有很大差异。这一观察结果表明，有 许多成功的抑制病毒感染的策略，就像已经进化出许多病毒拮抗剂一样 来干扰他们。有趣的是，虽然哺乳动物对病毒感染的细胞反应主要是 由 I 型干扰素 (IFN-I) 家族介导，我们最近描述了一种不依赖于 IFN-I 的防御 该系统涉及进化保守的 RNAse III 核酸酶。我们发现这种核酸酶，称为 Drosha， 响应病毒感染而快速移位至细胞质并形成高分子量结构 通过与 RNA 诱导的沉默复合物 (RISC) 结合，我们将其称为 ADAR-RISC 复合物 或者简单地说，ARC。在这里，我们寻求更好地了解这种复合物的生理相关性。

项目成果

ADAR1 Biology Can Hinder Effective Antiviral RNA Interference.

ADAR1 生物学可阻碍有效的抗病毒 RNA 干扰。

• 发表时间: 2023-04-27
• 作者: Uhl, Skyler;Jang, Chanyong;Frere, Justin J;Jordan, Tristan X;Simon, Anne E;tenOever, Benjamin R
• 通讯作者: tenOever, Benjamin R