Investigation of copper homeostasis mRNAs regulated by the Nonsense-mediated mRNA decay pathway
Investigation of copper homeostasis mRNAs regulated by the Nonsense-mediated mRNA decay pathway
批准号:
9232430
负责人:
Bessie W Kebaara
金额:
$41.29万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-16 至 2022-08-31
关键词:
AccountingAdverse effectsAffectCell physiologyCopperDataDegradation PathwayDrosophila genusEnvironmentEnvironmental ImpactGene ExpressionGene Expression RegulationGenesGoalsHereditary DiseaseHomeostasisHumanHuman GeneticsInvestigationKnowledgeLeadMediatingMessenger RNANonsense CodonNonsense MutationOrganismPathway interactionsPhysiologicalPlayProductionProteinsRegulationResearchRoleSaccharomyces cerevisiaeSystemTerminator CodonTestingTimeUntranslated RegionsWorkYeastsbaseenvironmental changefunctional groupinsightinterestmRNA DecaymRNA Transcript Degradationprematurepreventresponsetherapy developmenttranscription factor USFtranscriptome
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
The nonsense-mediated mRNA decay (NMD) pathway is a specialized pathway that contributes to the
recognition and rapid degradation of mRNA with premature termination codons. This prevents the
production of non-functional, potentially harmful truncated proteins. NMD affects the expression of a number
of human genetic diseases by modulating the expression of genes carrying nonsense mutations. NMD also
regulates the expression of specific genes by degrading natural mRNAs. Regulation of natural mRNAs by
NMD has been identified in numerous organisms ranging from yeast to humans. However, the extent and
reason for the targeting of most of these natural mRNAs is generally unknown and could be a way to
support a proper cellular response to changing environmental conditions. The objective of this study is to
investigate the role NMD plays in copper homeostasis. We hypothesize that mRNAs involved in copper
homeostasis and are sensitive to NMD are regulated by the pathway through similar features. In addition,
we postulate that the regulation of these mRNAs by NMD is responsive to environmental conditions. This
hypothesis is formulated based on our preliminary observations showing that four mRNAs involved in
copper homeostasis have identical NMD-targeting features. Additionally, regulation of one of the mRNAs by
NMD is responsive to environment copper levels. This research will determine the extent to which
functionally related mRNAs are regulated by NMD due to similar features. In addition, it will demonstrate the
extent to which this regulation is responsive to environmental conditions. We plan to test our central
hypothesis and accomplish the overall objective of this project by pursuing the following specific aims. In
Aim 1 we will determine the features/factors that target mRNAs involved in copper homeostasis to NMD. In
Aim 2 we will determine the environmental impact on the regulation of these mRNAs by NMD and the
physiological consequences resulting from this regulation The contributions of this research is that it will
demonstrate the extent to which natural mRNAs from the same functional group are regulated by NMD and
the influence the environment has on this regulation. Successful completion of these studies would
demonstrate for the first time the effect environmental conditions have on the regulation of functionally
related mRNAs by NMD. This knowledge will allow the categorization of cellular processes regulated NMD,
and lead to a more complete understanding of gene regulation in the genetically tractable organism S.
cerevisiae. It is important to understand natural mRNA regulation by NMD given that these mRNAs are
found in multiple organisms including humans and the strategies used by S. cerevisiae to regulate
functionally related mRNAs could be utilized in other systems and under other conditions. Furthermore, The
NMD pathway in humans is being targeted to treat genetic diseases caused by genes that contain
nonsense codons.
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