Cellular double-stranded RNA as a signal of stress, immunity, and aging.

细胞双链 RNA 作为压力、免疫和衰老的信号。

• 批准号: 8331579
• 负责人: Brenda L. Bass
• 金额: $ 74.73万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8331579
• 关键词: Aging; Aging-Related Process; Animal Model; Animals; Autoimmunity; Binding; Binding Proteins; Caenorhabditis elegans; Cells; Characteristics; Clinical; Detection; Diagnosis; Diagnostic; Disease; Double-Stranded RNA; Engineering; Gene Expression; Genome; Immunity; Knowledge; Longevity; Mammalian Cell; Mammals; Metabolic; Molecular Profiling; Monitor; Pathway interactions; Phenotype; Reagent; Research; Signal Transduction; Signaling Molecule; Source; Staging; Stress; Techniques; Testing; Viral; Virus Diseases; abstracting; computerized data processing; ds RNA-Binding Proteins; normal aging; overexpression; pathogen; public health relevance; research study; response

DESCRIPTION Abstract: In mammals, viral double-stranded RNA (dsRNA) triggers a response to pathogen by binding to host dsRNA binding proteins (dsRBPs). Increasingly, dsRBPs are also associated with diseased states, where a viral infection is not apparent, and the source of the dsRNA is unclear. The proposed research will explore the hypothesis that dsRNA transcribed from an animal's own genome is involved. In this model, an animal would have a characteristic pool of cellular dsRNA that would reflect metabolic state. Rapid and transient changes in dsRNA levels might occur during stress, or disease, while gradual changes during the lifetime of an animal would be part of the normal aging process. Studies to test the hypothesis will use the model organism C. elegans, as well as mammalian cells. Animals or cells will be engineered to overexpress dsRNA to test for a direct connection between levels of cellular dsRNA and the gene expression profiles and phenotypes associated with stress and aging. Sensitive high-throughput sequencing techniques will be used to identify the endogenous cellular dsRNA that serves to signal these processes. Identified cellular dsRNA and dsRBPs will be monitored for levels during stress or aging. Reagents for research and clinical purposes will be developed for the easy detection of dsRNA and to inhibit binding of dsRNAs to their target dsRBPs. The proposed experiments may uncover a previously unrecognized network of cellular dsRNA signaling molecules responsible for triggering pathways implicated in stress, autoimmunity and longevity, and set the stage for treatment and diagnosis of associated disease. Public Health Relevance: The proposed research may reveal that the causative agent in many diseased states is double-stranded RNA encoded by an animal's own genome. This knowledge would promote a huge shift in current paradigms and redirect research in ways that would accelerate progress in understanding disease and aging, and spur the search for diagnostic re

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