METTL3 in regulation of the aging process
METTL3 调节衰老过程
基本信息
- 批准号:10748833
- 负责人:
- 金额:--
- 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:2023-08-01 至 2023-08-02
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptedAffectAgingAnimal ModelAtrophicBindingBinding ProteinsBiologicalBiological ModelsCell physiologyComplexDataDependovirusDeteriorationEngineeringEnzymesEquilibriumEventExercise ToleranceFunctional disorderGene ExpressionGene Expression ProcessGenesGeneticGenetic TranscriptionGrowthHealthHomeostasisHypertrophyKnockout MiceLifeMaintenanceMediatingMediatorMessenger RNAMetabolicMethylationMethyltransferaseModelingModificationMolecularMorbidity - disease rateMovementMusMuscleMuscle functionMuscular AtrophyOrganPathologicPathway interactionsPhenotypePost-Transcriptional RegulationProcessProtein BiosynthesisProteomeQuality of lifeRNARNA methylationRNA-Binding ProteinsRegulationRibosomesRoleSignal TransductionSkeletal MuscleStimulusTestingTherapeuticTimeTranscriptional RegulationTranslatingTranslationsTropismagedcell ageclinically relevantexperimental studygain of functionhealthy agingin vivoinsightloss of functionmRNA Translationmedically necessary caremortalitymouse modelmuscle agingmuscle formnovelnovel strategiesoverexpressionposttranscriptionalpreservationpreventprogramsprospectiveprotein degradationreceptor expressionsarcopeniatoolwasting
项目摘要
PROJECT SUMMARY
Aging is a complex process where perturbation of multiple molecular pathways contributes to organ
deterioration and aging-related morbidity and mortality. One component of the aging process is severe
dysregulation of gene expression that contributes to changes in the proteome of aged cells, which can
compromise cell function. Understanding the mechanisms responsible for aging-induced perturbation of gene
expression will be key to develop the necessary medical therapies. Although significant progress has been
made in understanding the transcriptional changes occurring with aging, very little is known about how post-
transcriptional events, such as RNA modifications, control protein synthesis during aging. In this proposal we
will examine the role of METTL3-mediated m6A mRNA methylation in the context of aging using muscle aging
as a model system. We hypothesize that METTL3-dependent mRNA methylation regulates the process of
aging by controlling the translation of specific pro-hypertrophic mRNAs. For the first time, utilizing gain- and
loss-of-function approaches we will characterize this novel regulatory program by establishing the molecular
mechanisms by which m6A regulates the life of select mRNAs and assess the global aging- and METTL3-
dependent translation dynamics (aim 1), examining the therapeutic benefit of enhancing m6A content to
counteract sarcopenia in clinically relevant animal models (aim 2), and define the role of m6A binding proteins
in muscle aging (aim 3). Completion of the proposed aims will allow the uncovering of a novel mechanism
responsible for post-transcriptional regulation of aging with significant therapeutics ramifications.
项目总结
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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Federica Accornero其他文献
Federica Accornero的其他文献
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{{ truncateString('Federica Accornero', 18)}}的其他基金
Mechanistic characterization of a new master regulator of cardiac virus infections
心脏病毒感染新主调节因子的机制表征
- 批准号:
10255819 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Mechanistic characterization of a new master regulator of cardiac virus infections
心脏病毒感染新主调节因子的机制表征
- 批准号:
10455582 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Mechanistic characterization of a new master regulator of cardiac virus infections
心脏病毒感染新主调节因子的机制表征
- 批准号:
10045127 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Mechanistic characterization of a new master regulator of cardiac virus infections
心脏病毒感染新主调节因子的机制表征
- 批准号:
10672435 - 财政年份:2020
- 资助金额:
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8787792 - 财政年份:2013
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