Eukaryotic RNA NAD capping and deNADding
真核 RNA NAD 加帽和 deNADding
基本信息
- 批准号:10443996
- 负责人:
- 金额:$ 36.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-02-27 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAgingAmino AcidsAreaAssimilationsBacteriaBiologicalBiological ModelsBiological ProcessBiologyCOVID-19Cell NucleusCell physiologyCellsCellular StressComplexDNADataDiseaseElementsEnzymesEukaryotaEukaryotic CellExcisionGene ExpressionGrowthHomeostasisHumanIn VitroLinkMammalian CellMessenger RNAMetabolic stressMetabolismMitochondriaMitochondrial ProteinsMitochondrial RNAMolecularNicotinamide adenine dinucleotideNuclearNuclear DecayNuclear RNANutrientOrganismPathway interactionsPhysiologicalPlayPost-Transcriptional RegulationProcessPublishingRNARNA CapsRNA DecayRNA Polymerase IIRNA metabolismRNA vaccineRegulationResearchRespirationRoleSaccharomyces cerevisiaeSaccharomycetalesStarvationStressTestingTherapeuticTranscriptVirusWorkYeastsdecapping enzymedefined contributionepitranscriptomicsgenetic informationinsightmitochondrial dysfunctionnovelnovel strategiesnucleasepoly A specific exoribonucleaseresponsesenescencesugar
项目摘要
RNA 5′ end capping provides a layer of “epitranscriptomic” regulation, influencing numerous aspects of RNA
fate, including stability, processing, localization and translatability. Furthermore, enzymes that remove RNA
5′ end caps play critical roles in modulating these processes. Recently, a previously unknown form of RNA
5'-end capping has been identified in bacterial, yeast, and human cells. In this new form of RNA capping, the
metabolite nicotinamide adenine dinucleotide (NAD) is added at the RNA 5′ end. In contrast to 7-
methylguanylate (m7G) caps, which are added to mRNAs by a complex that associates with eukaryotic RNA
polymerase II (RNAP II), NAD caps are primarily added by RNAP itself in bacteria and eukaryotic nuclear and
mitochondrial transcripts. Thus, unlike m7G capping, which is observed in eukaryotes and certain eukaryotic
viruses, NAD capping is likely to occur in most, if not all, organisms. Our recently published work along with
our unpublished preliminary data, indicates that NAD capping targets mammalian RNAs for rapid decay. In
addition, we have shown eukaryotic cells possess several enzymes capable of removing NAD caps and,
furthermore, that the cellular functions of these “deNADding” enzymes are most evident during metabolic
stress. An overall theme emerging from our data is that addition and removal of NAD caps play critical roles
in mitochondrial function where NAD-capped mitochondrial-encoded transcripts and nuclear transcripts
encoding mitochondrial proteins are modulated by NAD caps. To decipher the interplay between cellular
assimilation of NAD and RNA metabolism we will define the functional role(s) of NAD caps and deNADding
enzymes in both budding yeast and mammalian cells. The first aim will investigate the hypothesis that NAD
capping of mitochondrial RNA plays a key role in maintaining NAD homeostasis with the NAD cap serving as
a reservoir to sequester and release free NAD for proper mitochondrial energetics. The second aim will
investigate the impact of NAD capping on nuclear encoded RNA and, in particular, explores the hypothesis
that NAD capping in budding yeast provides a mechanism for the targeted decay of RNAs in response to
nutrient stress. The third aim will determine how the NAD capping and deNADding of mammalian nuclear
mRNAs encoding mitochondrial proteins contributes to mitochondrial function upon cellular stress and
whether perturbation of the deNADding of these mRNAs contributes to mitochondrial dysfunction associated
with aging. The proposed studies will provide new insight in an emerging area of RNA biology, post-
transcriptional regulation in cellular metabolism and, furthermore, may provide a mechanistic framework for
developing new approaches to control gene expression in normal and disease states.
RNA 5 '端帽提供了一层“表转录组”调控,影响RNA的许多方面
项目成果
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MEGERDITCH KILEDJIAN其他文献
MEGERDITCH KILEDJIAN的其他文献
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{{ truncateString('MEGERDITCH KILEDJIAN', 18)}}的其他基金
Eukaryotic RNA NAD capping and deNADding
真核 RNA NAD 加帽和 deNADding
- 批准号:
10797880 - 财政年份:2018
- 资助金额:
$ 36.51万 - 项目类别:
Eukaryotic RNA NAD capping and deNADding
真核 RNA NAD 加帽和 deNADding
- 批准号:
10622526 - 财政年份:2018
- 资助金额:
$ 36.51万 - 项目类别:
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