tRNA processing and nuclear-cytoplasmic dynamics
tRNA 加工和核质动力学
基本信息
- 批准号:10473791
- 负责人:
- 金额:$ 34.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-05-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:Adaptor Signaling ProteinAddressAffectAmino AcidsAnilineApoptosis Regulation GeneArchaeaBackBiochemicalBiologicalBiological AssayBiological ProcessBiologyCell NucleusCellsCodeCodon NucleotidesComplexCytoplasmDataDefectDiseaseEnsureEquilibriumEukaryotic CellExcisionExplosionExportinsFamilyFormaldehydeGene ExpressionGene MutationGenesGeneticGenetic TranscriptionGenetic studyGenomeGenomicsGrowthHealthHumanImportinsIndividualIntronsKnowledgeLearningLicensingMalignant NeoplasmsMessenger RNAMetabolic DiseasesMethodologyMicroscopyModificationMolecularMovementNeuromuscular DiseasesNuclearNuclear ExportNuclear ImportNuclear ProteinNutrientOrganismPathway interactionsPhenylalanine-Specific tRNAPlayProceduresProcessProteinsProteomeQuality ControlRNARNA ProcessingRNA SplicingRegulationRegulator GenesReportingResearchResearch Project SummariesRibosomesRoleSaccharomycetalesSignal TransductionSpecific qualifier valueSpecificityStressStretchingTechnologyTestingTimeTransfer RNATranslatingTranslationsTravelUntranslated RNAVertebratesYeast Model SystemYeastsbasecell preparationcrosslinkgene productgenome wide screenhuman diseasein vivomRNA StabilitymutantnovelnucleasepreferenceprogramsresponsetRNA Precursortrafficking
项目摘要
Project Summary
This research program focuses on tRNA biology and its subcellular trafficking. tRNAs are small noncoding RNAs
that are essential for decoding the genome by delivering amino acids to translating ribosomes according to codon
directions in mRNAs. Defects in tRNA biology cause numerous human disorders from metabolic diseases, to
neuromuscular diseases, and to cancer. tRNA biology requires a complex set of conserved gene products for
post-transcriptional processing, subcellular traffic, and intron turnover. We employ budding yeast and in vivo
technologies to discover unknown important aspects of tRNA biology. In Aim 1 of this proposal we will study
tRNA nuclear export. It is not completely understood how tRNAs that are transcribed and partially processed in
the nucleus are exported to the cytoplasm for their iterative function in translation. One pathway utilizes the
conserved b-importin Los1/Exportin that is dedicated to tRNA nuclear export, but it is unessential in all tested
organisms. Employing an unbiased genome-wide screen for gene products involved in tRNA biology, we
discovered three additional gene products that export tRNA to the cytoplasm: the heterodimer, Mex67-Mtr2 and
Crm1. However, Mex67-Mtr2 and Crm1 are not dedicated to tRNA and they have major roles in mRNA and
protein nuclear export. Thus, it is not understood how they recognize tRNAs. Moreover, Mex67-Mtr2 appears to
be error-prone, delivering tRNA to the cytoplasm prior to removal of leader/trailer sequences. We will identify
adapters needed to complex Mex67-Mtr2 and Crm1 with tRNAs and learn how mistakes by the error-prone
exporters are dealt with. In Aim2 of this proposal we will study trafficking of tRNAs between the nucleus and the
cytoplasm. Although for decades it was thought that tRNA movement is unidirectional, nucleus to cytoplasm, we
co-discovered that tRNAs move bi-directionally between the nucleus and the cytoplasm and that the dynamics
are conserved between yeast and vertebrate cells. We developed a new methodology, the HCl/aniline assay,
that reports tRNA retrograde nuclear import and re-export to the cytoplasm. We will employ this methodology to
characterize the gene products that function in the tRNA retrograde pathway and assess whether tRNA
retrograde traffic is iterative. Aim 3 addresses tRNA introns. Possession of tRNA introns in subsets of tRNA
genes is conserved from Archaea to humans. Although the mechanism to remove introns from pre-tRNAs is
understood, the fate and function of tRNA introns is largely mysterious. We discovered one mechanism for tRNA
intron turnover; however, there are at least four additional unknown mechanisms to destroy tRNA introns which
we propose to characterize. Surprisingly, we also learned that under particular stresses, tRNA introns
accumulate to high levels. Furthermore, tRNA introns contain long stretches of complementarity to mRNAs. Our
preliminary data support the hypothesis that they regulate gene express through complementary base paring
with mRNAs; we will test this hypothesis in Aim 3. Thus, the proposed research program impacts upon multiple
facets of gene expression, quality control, and issues important to human health.
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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Anita K Hopper其他文献
Anita K Hopper的其他文献
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{{ truncateString('Anita K Hopper', 18)}}的其他基金
tRNA processing and nuclear-cytoplasmic dynamics
tRNA 加工和核质动力学
- 批准号:
9920190 - 财政年份:2017
- 资助金额:
$ 34.07万 - 项目类别:
tRNA processing and nuclear-cytoplasmic dynamics
tRNA 加工和核质动力学
- 批准号:
9284086 - 财政年份:2017
- 资助金额:
$ 34.07万 - 项目类别:
tRNA processing and nuclear-cytoplasmic dynamics
tRNA 加工和核质动力学
- 批准号:
10296430 - 财政年份:2017
- 资助金额:
$ 34.07万 - 项目类别:
YEAST GENES IN RNA PROCESSING & NUCLEUS/CYTOSOL EXCHANGE
RNA 加工中的酵母基因
- 批准号:
7907380 - 财政年份:2009
- 资助金额:
$ 34.07万 - 项目类别:
YEAST GENES IN RNA PROCESSING & NUCLEUS/CYTOSOL EXCHANGE
RNA 加工中的酵母基因
- 批准号:
2389488 - 财政年份:1979
- 资助金额:
$ 34.07万 - 项目类别:
MUTATIONS AFFECTING THE PRODUCTION OF MATURE RNAS
影响成熟 RNA 产生的突变
- 批准号:
3275156 - 财政年份:1979
- 资助金额:
$ 34.07万 - 项目类别:
MUTATIONS AFFECTING THE PRODUCTION OF MATURE RNAS
影响成熟 RNA 产生的突变
- 批准号:
3275164 - 财政年份:1979
- 资助金额:
$ 34.07万 - 项目类别:
MUTATIONS AFFECTING THE PRODUCTION OF MATURE RNAS
影响成熟 RNA 产生的突变
- 批准号:
3275161 - 财政年份:1979
- 资助金额:
$ 34.07万 - 项目类别:
YEAST GENES IN RNA PROCESSING & NUCLEUS/CYTOSOL EXCHANGE
RNA 加工中的酵母基因
- 批准号:
7148140 - 财政年份:1979
- 资助金额:
$ 34.07万 - 项目类别:
YEAST GENES IN RNA PROCESSING & NUCLEUS/CYTOSOL EXCHANGE
RNA 加工中的酵母基因
- 批准号:
7477593 - 财政年份:1979
- 资助金额:
$ 34.07万 - 项目类别:
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