Understanding double-stranded RNA recognition in human cells
了解人体细胞中的双链 RNA 识别
基本信息
- 批准号:10715297
- 负责人:
- 金额:$ 41.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-04 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:Antiviral ResponseAutoimmune DiseasesBiochemicalBiogenesisBiological ProcessCellsCommunicable DiseasesComplexDevelopmentDiseaseDouble-Stranded RNAEnsureGenetic screening methodGoalsHumanHuman GenomeImmuneImmune responseImmunologic StimulationLigandsMalignant NeoplasmsMethodsMicroRNAsMicroprocessorModelingNatural ImmunityProteinsRegulationResearchStructureTherapeuticTranscriptViralVirusautoinflammatory diseasesbiochemical modelds RNA-Binding Proteinshuman modelinnate immune sensinginsightpreventsensorsingle molecule
项目摘要
PROJECT SUMMARY
Specific recognition of double-stranded RNA (dsRNA) structures underlies key biological
processes from development to antiviral immune responses, and involves a host of dsRNA-
binding proteins. Biochemical and structural studies have delineated how these proteins interact
with model ligands, yet dsRNAs that they encounter in cells are far more complex. Moreover, little
is known about how cells regulate dsRNA recognition. The goal of my lab is to understand how
dsRNA-binding proteins interact with natural dsRNAs in cells, connecting biochemical models of
dsRNA recognition to cellular dsRNA recognition and regulation. In the next five years, we will
focus on dsRNA recognition in microRNA (miRNA) biogenesis and innate immune sensing.
During miRNA biogenesis, Microprocessor recognizes and cleaves hairpin-like structures from
long transcripts called primary miRNAs (pri-miRNAs). My previous research built a unifying model
of human pri-miRNA and discovered that an optimal miRNA hairpin enhances the cleavage of a
suboptimal miRNA hairpin on the same transcript—known as cluster assistance. Because nearly
40% of human miRNAs reside in clusters, with many implicated in diseases and influenced by
cluster assistance, we propose to dissect this fundamental regulatory mechanism in miRNA
biogenesis using biochemical, single-molecule, and structural approaches. Recognition of dsRNA
by innate immune sensors such as RIG-I and MDA5 initiates antiviral responses. Recent studies
show that endogenous dsRNAs can also activate these sensors, sometimes resulting in
autoinflammatory and autoimmune diseases. The recognition of self dsRNAs therefore needs to
be restricted by proteins that modify, degrade or shield endogenous dsRNAs. Building on our
expertise in dsRNA recognition and processing, we will 1) develop new biochemical methods to
identify dsRNA ligands of innate immune sensors, and 2) develop new genetic screen methods
to identify factors that restrict self dsRNA sensing in innate immunity. Together these studies will
provide crucial insights into how cellular dsRNAs are sensed and regulated, with therapeutic
implications for cancer, autoimmune and infectious diseases.
项目总结
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Wenwen Fang其他文献
Wenwen Fang的其他文献
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{{ truncateString('Wenwen Fang', 18)}}的其他基金
Dissecting the regulation of RNA sensing in innate immunity
剖析先天免疫中 RNA 传感的调节
- 批准号:
10456287 - 财政年份:2017
- 资助金额:
$ 41.88万 - 项目类别:
Dissecting the regulation of RNA sensing in innate immunity
剖析先天免疫中 RNA 传感的调节
- 批准号:
10402427 - 财政年份:2017
- 资助金额:
$ 41.88万 - 项目类别:
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