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.

项目总结