Elucidating roles and mechanisms of double-stranded RNA-mediated pathways
阐明双链RNA介导途径的作用和机制
基本信息
- 批准号:10594483
- 负责人:
- 金额:$ 60.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AnimalsAntiviral ResponseBinding ProteinsBiochemicalBiochemistryCaenorhabditis elegansDeaminationDicer EnzymeDouble-Stranded RNAEnabling FactorsEnzymesGene SilencingGenetic ScreeningGoalsHealthHumanImmuneImmune responseIn VitroInnate Immune ResponseInterferonsInvertebratesKineticsKnowledgeMammalsMediatingMolecularMolecular MotorsPathway interactionsProcessProteinsRNARNA EditingRNA InterferenceRNA Interference PathwayResearchRoleSiteSmall RNAVertebratesViraldesigndsRNA adenosine deaminasefascinatehelicasein vivo evaluationinsightmodel organismstructural biologyviral RNA
项目摘要
SUMMARY/ABSTRACT
The goal of the proposed research is to define and characterize the long double-stranded RNA (dsRNA) encoded
and expressed in animals, including humans, and the proteins that bind, modify, and process this dsRNA. A key,
health-related, focus is how this endogenous dsRNA is discriminated from the long viral dsRNA that is recognized
as foreign to trigger an innate immune response. Recent studies show that in both vertebrates and invertebrates,
the RNA editing enzymes called Adenosine deaminases that act on RNA, or ADARs, deaminate endogenous
dsRNA so that it will not trigger an aberrant immune response. The mechanism by which ADARs, and the editing
sites they create, preclude activation of an innate immune response is unclear, and the proposed research is
designed to fill this gap in knowledge. Using genetic screens and molecular approaches, the model organism C.
elegans will be used to discover RNAs and proteins that lead to an immune response in strains lacking ADARs;
biochemical approaches will be used to provide in-depth mechanistic insights. While mammals use the interferon
pathway to mount an antiviral response, invertebrates lack this pathway, and instead, use RNA interference
(RNAi) in antiviral defense. The enzyme Dicer is key to the antiviral RNAi pathway and is essential for cleaving
viral dsRNA during the invertebrate immune response. Our prior in vitro studies indicate Dicer's helicase domain
recognizes the ends of viral dsRNA as “nonself”, or foreign, and the proposed studies are designed to test this
in vivo. The helicase domain of invertebrate Dicers is a fascinating molecular motor, and biochemistry, transient
kinetic analyses, and structural biology, will be used to understand how it coordinates dsRNA cleavage, and
ultimately passes small RNA products to downstream factors that enable gene silencing by the RNAi pathway.
Modulation of Dicer's activity by accessory factors that interact with the helicase domain will be investigated.
Differences in activities of the helicase domain of human Dicer and invertebrate Dicers will be explored to
understand how this enzyme evolved as the immune pathways of vertebrates and invertebrates diverged.
摘要/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Brenda L. Bass其他文献
Activation of PKR by a short-hairpin RNA
短发夹 RNA 激活 PKR
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Kyle A. Cottrell;Sua Ryu;H. Donelick;Hung Mai;Jackson R. Pierce;Brenda L. Bass;Jason D. Weber - 通讯作者:
Jason D. Weber
The short answer
简短的回答
- DOI:
10.1038/35078175 - 发表时间:
2001-05-24 - 期刊:
- 影响因子:48.500
- 作者:
Brenda L. Bass - 通讯作者:
Brenda L. Bass
The competitive landscape of the dsRNA world
DSRNA世界的竞争格局
- DOI:
10.1016/j.molcel.2023.11.033 - 发表时间:
2024-01-04 - 期刊:
- 影响因子:16.600
- 作者:
Kyle A. Cottrell;Ryan J. Andrews;Brenda L. Bass - 通讯作者:
Brenda L. Bass
Brenda L. Bass的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Brenda L. Bass', 18)}}的其他基金
Elucidating roles and mechanisms of double-stranded RNA-mediated pathways
阐明双链RNA介导途径的作用和机制
- 批准号:
10795249 - 财政年份:2021
- 资助金额:
$ 60.39万 - 项目类别:
Elucidating roles and mechanisms of double-stranded RNA-mediated pathways
阐明双链RNA介导途径的作用和机制
- 批准号:
10380082 - 财政年份:2021
- 资助金额:
$ 60.39万 - 项目类别:
Elucidating roles and mechanisms of double-stranded RNA-mediated pathways
阐明双链RNA介导途径的作用和机制
- 批准号:
10189022 - 财政年份:2021
- 资助金额:
$ 60.39万 - 项目类别:
Unlocking evolutionarily latent immune functions for treating disease
解锁进化上潜在的免疫功能来治疗疾病
- 批准号:
10021943 - 财政年份:2020
- 资助金额:
$ 60.39万 - 项目类别:
Unlocking evolutionarily latent immune functions for treating disease
解锁进化上潜在的免疫功能来治疗疾病
- 批准号:
10240664 - 财政年份:2020
- 资助金额:
$ 60.39万 - 项目类别:
Unlocking evolutionarily latent immune functions for treating disease
解锁进化上潜在的免疫功能来治疗疾病
- 批准号:
10700046 - 财政年份:2020
- 资助金额:
$ 60.39万 - 项目类别:
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:
8706759 - 财政年份:2011
- 资助金额:
$ 60.39万 - 项目类别:
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:
8142547 - 财政年份:2011
- 资助金额:
$ 60.39万 - 项目类别:
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 - 财政年份:2011
- 资助金额:
$ 60.39万 - 项目类别:
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:
8520153 - 财政年份:2011
- 资助金额:
$ 60.39万 - 项目类别:
相似海外基金
Regulation of RIG-I mediated antiviral response upon influenza A virus infection
RIG-I介导的甲型流感病毒感染抗病毒反应的调节
- 批准号:
494286 - 财政年份:2023
- 资助金额:
$ 60.39万 - 项目类别:
Operating Grants
Activation of the DNA-PK-dependent antiviral response as a novel cancer immunotherapy
激活 DNA-PK 依赖性抗病毒反应作为一种新型癌症免疫疗法
- 批准号:
10364056 - 财政年份:2022
- 资助金额:
$ 60.39万 - 项目类别:
ADAR1-mediated antiviral response in Zika virus (ZIKV) infection
ADAR1 介导的寨卡病毒 (ZIKV) 感染抗病毒反应
- 批准号:
10621913 - 财政年份:2022
- 资助金额:
$ 60.39万 - 项目类别:
ADAR1-mediated antiviral response in Zika virus (ZIKV) infection
ADAR1 介导的寨卡病毒 (ZIKV) 感染抗病毒反应
- 批准号:
10373627 - 财政年份:2022
- 资助金额:
$ 60.39万 - 项目类别:
Activation of the DNA-PK-dependent antiviral response as a novel cancer immunotherapy
激活 DNA-PK 依赖性抗病毒反应作为一种新型癌症免疫疗法
- 批准号:
10553146 - 财政年份:2022
- 资助金额:
$ 60.39万 - 项目类别:
Mechanisms of IgE-mediated regulation of monocyte antiviral response pathways
IgE介导的单核细胞抗病毒反应途径的调节机制
- 批准号:
10640247 - 财政年份:2021
- 资助金额:
$ 60.39万 - 项目类别:
Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infection
AMPK 和 Hippo 信号传导之间的相互作用调节眼部对寨卡病毒感染的抗病毒反应
- 批准号:
10322026 - 财政年份:2021
- 资助金额:
$ 60.39万 - 项目类别:
Mechanisms of IgE-mediated regulation of monocyte antiviral response pathways
IgE 介导的单核细胞抗病毒反应途径调节机制
- 批准号:
10438876 - 财政年份:2021
- 资助金额:
$ 60.39万 - 项目类别:
Antiviral response coupled with transposon derepression in Alzheimer's disease and aging
抗病毒反应与转座子去抑制在阿尔茨海默病和衰老中的作用
- 批准号:
10629440 - 财政年份:2021
- 资助金额:
$ 60.39万 - 项目类别:
Epigenetic Control of Mucosal IRF1/IFN-III Antiviral Response by Enhancer-like Promoter and its Coding lncRNA
增强子样启动子及其编码lncRNA对粘膜IRF1/IFN-III抗病毒反应的表观遗传控制
- 批准号:
10373575 - 财政年份:2021
- 资助金额:
$ 60.39万 - 项目类别: