Viral modulation of epitranscriptomic mechanisms
表观转录组机制的病毒调节
基本信息
- 批准号:10317748
- 负责人:
- 金额:$ 0.48万
- 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:2021-05-19 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenovirus InfectionsAdenovirusesAffinityAffinity ChromatographyAmino AcidsAntibodiesBindingBinding ProteinsBiochemicalBiologicalBiological AssayBiological ModelsBiologyCell NucleusCell physiologyCellsCellular biologyChemicalsDNA VirusesDataDetectionDiseaseDouble Stranded DNA VirusGeneticGenetic TranscriptionGoalsGrowthHost DefenseHumanImmune responseImmune systemIndividualInfectionInhibitor of Differentiation ProteinsInnate Immune ResponseKnowledgeLifeMapsMass Spectrum AnalysisMeasuresMediatingMessenger RNAMethodsModificationNuclearNuclear ExportOligonucleotidesOrganPathway interactionsPhysiologic pulsePost-Transcriptional RNA ProcessingProcessProductionProteinsProteomicsRNARNA ProcessingRNA SequencesRNA SplicingRNA analysisRNA metabolismRNA-Binding ProteinsRNA-Protein InteractionReaderRegulationRespiratory Tract InfectionsRoleStable Isotope LabelingStudy modelsSystemTechnologyTertiary Protein StructureTimeTranslatingTranslationsUntranslated RNAViralViral GenesVirusVirus Diseasesbasecombatepitranscriptomeepitranscriptomicsgene producthuman diseasehuman pathogenimprovednew technologyprotein complexprotein expressiontooltranscriptome sequencingviral RNAvirus host interaction
项目摘要
PROJECT SUMMARY
The overall goal of this proposal is to develop high-throughput mass spectrometry technologies applied to the
study of post-transcriptional RNA modifications (PTrMs) and associations with RNA binding proteins (RBPs).
Efficient RNA processing and protein translation requires interactions with numerous RNA binding proteins, and
can be regulated by chemical RNA modifications. PTrMs have been implicated in such diverse processes as
RNA splicing, nuclear export, stability, and translation. The mechanisms by which PTrMs control RNA fate has
opened up a new field dubbed “Epitranscriptomics”. Although there are antibody approaches to detect some
modifications, there is a need for orthogonal approaches for unbiased identification and analysis of PTrMs. Since
small DNA viruses that replicate in the nucleus have both to employ cellular machinery to transcribe and translate
their gene products, and also develop ways to counteract host defenses, these viruses harness and manipulate
cellular RNA processing pathways. Virus infections thus provide elegant biological models to decipher how RNA
transcription and its chemical modifications can be regulated and exploited to direct the host cell machinery
towards production of viral progeny. Based on preliminary data generated by our collaborative team, our
objectives in this proposal are to employ Adenovirus as a model system to study PTrMs on non-coding and
messenger viral RNAs and how they are exploited to counter host defenses and promote efficient viral RNA
processing and progeny production. Adenoviruses are large non-eveloped viruses and include over 50 distinct
strains which elicit a wide range of effects in humans, from respiratory infections to life-threatening organ
problems in people with weakened immune systems. Adenoviruses hijack the host cell machinery to express
viral genes, and this is achieved by overtaking RNA-mediated processes. Our preliminary data show how
Adenovirus infection exploits the m6A modification on RNA to promote splicing and also alters RNA-protein
interactions. Here we will develop improved mass spectrometry (MS) technologies to quantitatively and
comprehensively detect RNA modifications and RNA-protein interactions over a detailed time-course of infection.
Our MS technology will be paired with cellular and genetic assays to determine how the modifications are utilized
by Adenovirus to promote growth and counter host defenses in ways that culminate in human disease. These
high-throughput unbiased MS-based technologies and approaches will be broadly applicable to enable new
biology in virus-host interactions and epitranscriptomics.
项目摘要
该提案的总体目标是开发应用于生物样品的高通量质谱技术。
研究转录后RNA修饰(PTrM)和与RNA结合蛋白(RBP)的关系。
有效的RNA加工和蛋白质翻译需要与许多RNA结合蛋白相互作用,
可以通过化学RNA修饰来调节。PTrMs涉及多种过程,
RNA剪接、核输出、稳定性和翻译。PTrMs控制RNA命运的机制
开辟了一个新的领域,被称为“外延脚本学”。虽然有抗体方法来检测一些
修改,需要正交方法来无偏地识别和分析PTrM。以来
在细胞核中复制的小DNA病毒必须利用细胞机制来转录和翻译
它们的基因产物,并开发出对抗宿主防御的方法,这些病毒利用和操纵
细胞RNA加工途径。因此,病毒感染提供了优雅的生物学模型,以破译RNA
转录及其化学修饰可以被调节和利用来指导宿主细胞机制
产生病毒后代。根据我们合作团队生成的初步数据,
本提案的目的是采用腺病毒作为模型系统,研究非编码和
信使病毒RNA以及它们如何被利用来对抗宿主防御并促进有效的病毒RNA
加工和后代生产。腺病毒是大型非进化病毒,包括50多种不同的腺病毒。
在人类中引起广泛影响的菌株,从呼吸道感染到危及生命的器官
免疫系统较弱的人的问题。腺病毒劫持宿主细胞机器表达
病毒基因,这是通过超越RNA介导的过程来实现的。我们的初步数据显示
腺病毒感染利用RNA上的m6 A修饰来促进剪接并改变RNA蛋白
交互.在这里,我们将开发改进的质谱(MS)技术,以定量和
在感染的详细时间过程中全面检测RNA修饰和RNA-蛋白质相互作用。
我们的MS技术将与细胞和遗传分析配对,以确定如何利用修改
通过腺病毒来促进生长和对抗宿主防御,最终导致人类疾病。这些
高通量无偏MS技术和方法将广泛适用于实现新的
病毒-宿主相互作用和表观转录组学中的生物学。
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)
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Benjamin A Garcia其他文献
Microbiota-dependent histone butyrylation in the mammalian intestine
哺乳动物肠道中微生物群依赖性组蛋白丁酰化
- DOI:
10.1101/2022.09.29.510184 - 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
Leah A. Gates;B. Reis;P. Lund;M. Paul;M. Leboeuf;Zara Nadeem;T. Carroll;Benjamin A Garcia;D. Mucida;C. Allis - 通讯作者:
C. Allis
Proteotranscriptomic Strategy to Discover Acute Myeloid Leukemia Immunotherapy Targets
- DOI:
10.1182/blood-2022-167378 - 发表时间:
2022-11-15 - 期刊:
- 影响因子:
- 作者:
Lusha Cao;Yang Xu;Tina Glisovic-Aplenc;Kevin Nestler;Saar Gill;Kathrin M. Bernt;Benjamin A Garcia;Hossein Fazelinia;Lingyu Guan;Yi Xing;Richard Aplenc - 通讯作者:
Richard Aplenc
The cerebral cavernous malformation pathway controls embryonic endocardial gene expression through regulation of MEKK3 signaling and KLF expression
脑海绵状血管瘤通路通过调节MEKK3信号和KLF表达来控制胚胎心内膜基因表达
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
Zinan Zhou;David R. Rawnsley;Lauren M. Goddard;Wei Pan;Xing;Zoltán;Jakus;Hui Zheng;Jisheng Yang;S. Arthur;K. Whitehead;Dean Y Li;Bin;Zhou;Benjamin A Garcia;Xiangjian Zheng;M. Kahn - 通讯作者:
M. Kahn
RNA Modifications on Long Non-Coding RNAs in Multiple Myeloma
- DOI:
10.1182/blood-2024-207137 - 发表时间:
2024-11-05 - 期刊:
- 影响因子:
- 作者:
Catheryn Bolick;Prasanth Thunuguntla;Dakota Colbert;Steve Daly;Yash Rajana;Jaiyana King;Matthew Mueller;Dhanusha Duraiyan;Benjamin A Garcia;John F. DiPersio;Jessica Silva-Fisher - 通讯作者:
Jessica Silva-Fisher
Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree
新型线粒体DNA导致抽动秽语症谱系的结缔组织疾病
- DOI:
10.1101/2022.02.25.481696 - 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
Patrick M. Schaefer;Leonardo Scherer Alves;M. Lvova;Jessica Huang;K. Rathi;Kevin A. Janssen;Arrienne Butic;T. Yardeni;Ryan M. Morrow;M. Lott;Kierstin N Keller;Benjamin A Garcia;C. Francomano;D. Wallace - 通讯作者:
D. Wallace
Benjamin A Garcia的其他文献
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{{ truncateString('Benjamin A Garcia', 18)}}的其他基金
Quantitative mass spectrometry for comprehending epigenetic mechanisms in a new underlying neurological developmental disorder
定量质谱分析用于理解新的潜在神经发育障碍的表观遗传机制
- 批准号:
10515832 - 财政年份:2022
- 资助金额:
$ 0.48万 - 项目类别:
Quantitative mass spectrometry for comprehending epigenetic mechanisms in a new underlying neurological developmental disorder
定量质谱分析用于理解新的潜在神经发育障碍的表观遗传机制
- 批准号:
10684772 - 财政年份:2022
- 资助金额:
$ 0.48万 - 项目类别:
Cocaine-induced histone post-translational modifications
可卡因诱导的组蛋白翻译后修饰
- 批准号:
9304987 - 财政年份:2016
- 资助金额:
$ 0.48万 - 项目类别:
Shared Resources Core 2: Quantitative Proteomics Core
共享资源核心 2:定量蛋白质组学核心
- 批准号:
10269910 - 财政年份:2015
- 资助金额:
$ 0.48万 - 项目类别:
Shared Resources Core 2: Quantitative Proteomics Core
共享资源核心 2:定量蛋白质组学核心
- 批准号:
10024849 - 财政年份:2015
- 资助金额:
$ 0.48万 - 项目类别:
Viral modulation of epitranscriptomic mechanisms
表观转录组机制的病毒调节
- 批准号:
10606522 - 财政年份:2015
- 资助金额:
$ 0.48万 - 项目类别:
Viral modulation of epitranscriptomic mechanisms
表观转录组机制的病毒调节
- 批准号:
10455807 - 财政年份:2015
- 资助金额:
$ 0.48万 - 项目类别:
Viral modulation of epitranscriptomic mechanisms
表观转录组机制的病毒调节
- 批准号:
10407654 - 财政年份:2015
- 资助金额:
$ 0.48万 - 项目类别:
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