Prion-based regulation of RNA-modifying enzyme activities
基于朊病毒的 RNA 修饰酶活性调节
基本信息
- 批准号:10799089
- 负责人:
- 金额:$ 3.02万
- 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:2021-08-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdoptedAffectAgingBehaviorBiochemicalBiologyBrain DiseasesCatalysisCell ProliferationCell SurvivalCell physiologyCellsChemicalsDiseaseEnzymesEpigenetic ProcessFluorescence MicroscopyGene ExpressionGeneticGoalsGrowthHealthHeredityHeritabilityHigh-Throughput Nucleotide SequencingHumanLifeMethodsModificationMolecularMolecular ConformationPhenotypePrPPrionsProtein BiosynthesisPseudouridineRNARNA ConformationRegulationResearchResistanceRoleSaccharomycetalesStressStructureWorkcell growthenzyme activityprion-basedprion-liketrait
项目摘要
Project Summary/Abstract
Prion proteins are notorious in biology for causing deadly, infectious brain diseases.
Beyond disease, however, prions completely altered our understanding of heredity, and
contrary to their reputation, they are not only disease-causing agents. Instead, they are
found across kingdoms of life, and are an epigenetic mechanism that affects a panoply
of cellular processes, also producing biologically beneficial traits. In this proposal we
focus on prions that regulate RNA, specifically, prionogenic conformations of RNA-
modifying enzymes. These highly conserved enzymes catalyze numerous chemical
modifications on RNA that are critical for their structure and function. The goal of our
research is to understand how prion-like forms of these enzymes may alter their activities
on RNA, producing changes to gene expression, and ultimately, leading to long-lasting,
heritable growth phenotypes, such as resistance to environmental stress. One recent
such example that we have detailed is a prionogenic form of a pseudouridine synthase,
which affects cell proliferation, aging, and protein synthesis. This work led us to
investigate the capacity for other RNA-modifying enzymes to have prion-like behavior,
and we now have several new examples for study. In this proposal, we will investigate
whether RNA modifications are changed when the enzymes that make them adopt prion-
like conformations, the effects these changes have on gene expression, the role for
enzyme catalysis, the structure of the infectious prion protein, and whether the prion-
based behavior that we have observed in budding yeast is conserved in human cells. We
approach these questions using a combination of genetics, high-throughput sequencing,
classical biochemical methods, and fluorescence microscopy. In summary, this work aims
to uncover the molecular details of epigenetic, prion-based regulation of RNA that affects
cell growth and survival.
项目总结/摘要
朊病毒蛋白质在生物学上因导致致命的传染性脑部疾病而臭名昭著。
然而,除了疾病,朊病毒完全改变了我们对遗传的理解,
与它们的名声相反,它们不仅是致病因素。取而代之的是
在生命王国中都能找到,是一种影响一整套
细胞过程,也产生生物学上有益的性状。在本提案中,我们
专注于朊病毒,调节RNA,特别是RNA的朊病毒构象-
修饰酶这些高度保守的酶催化许多化学物质,
RNA上的修饰对其结构和功能至关重要。我们的目标
研究的目的是了解这些酶的朊病毒样形式如何改变它们的活性
RNA上,产生基因表达的变化,并最终导致长期的,
可遗传的生长表型,如对环境胁迫的抗性。最近的一
我们详细介绍的例子是假尿苷合酶的朊病毒原形式,
影响细胞增殖、衰老和蛋白质合成。这项工作使我们
研究其他RNA修饰酶具有朊病毒样行为的能力,
我们现在有几个新的例子可以研究。在这份提案中,我们将调查
当使它们接受朊病毒的酶时,RNA修饰是否发生了变化,
像构象一样,这些变化对基因表达的影响,
酶催化,感染性朊病毒蛋白的结构,以及朊病毒-
我们在芽殖酵母中观察到的基本行为在人类细胞中是保守的。我们
通过结合遗传学,高通量测序,
经典的生物化学方法和荧光显微镜。总之,这项工作的目的是
揭示了表观遗传的分子细节,朊病毒为基础的RNA调节,
细胞生长和存活。
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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David M. Garcia其他文献
A Prion that regulates genome diversification
调节基因组多样化的朊病毒
- DOI:
10.1101/2021.10.23.465590 - 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
James S. Byers;Raymond A. Futia;Alex Van Elgort;Thomas M Lozanoski;David M. Garcia;Daniel F. Jarosz - 通讯作者:
Daniel F. Jarosz
The Importance of RNA Pairing Stability and Target Concentration for Regulation by MicroRNAs
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:0
- 作者:
David M. Garcia - 通讯作者:
David M. Garcia
David M. Garcia的其他文献
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{{ truncateString('David M. Garcia', 18)}}的其他基金
Prion-based regulation of RNA-modifying enzyme activities
基于朊病毒的 RNA 修饰酶活性调节
- 批准号:
10618332 - 财政年份:2021
- 资助金额:
$ 3.02万 - 项目类别:
Prion-based regulation of RNA-modifying enzyme activities
基于朊病毒的 RNA 修饰酶活性调节
- 批准号:
10277361 - 财政年份:2021
- 资助金额:
$ 3.02万 - 项目类别:
Prion-based regulation of RNA-modifying enzyme activities
基于朊病毒的 RNA 修饰酶活性调节
- 批准号:
10453589 - 财政年份:2021
- 资助金额:
$ 3.02万 - 项目类别:
Heritable protein aggregation affecting genome preservation and RNA regulation
影响基因组保存和 RNA 调控的遗传蛋白聚集
- 批准号:
8782989 - 财政年份:2014
- 资助金额:
$ 3.02万 - 项目类别:
Heritable protein aggregation affecting genome preservation and RNA regulation
影响基因组保存和 RNA 调控的遗传蛋白聚集
- 批准号:
8954976 - 财政年份:2014
- 资助金额:
$ 3.02万 - 项目类别:
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