tRNA processing and nuclear-cytoplasmic dynamics
tRNA 加工和核质动力学
基本信息
- 批准号:9920190
- 负责人:
- 金额:$ 32.76万
- 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 2021-08-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAnabolismApoptosisAreaBackBiochemicalBiogenesisBiologicalBiological ProcessBiologyCell NucleusCellsComplexCytoplasmCytoplasmic ProteinCytoskeletonDataDefectDiseaseEventExportinsGene ExpressionGene MutationGenesGeneticGenetic TranscriptionGenetic studyGenomeGenomicsHealthHumanLearningMalignant NeoplasmsMediatingMessenger RNAMetabolic DiseasesMethodologyMitochondriaMitochondrial Membrane ProteinModelingMovementMutationMyosin Type VNeuromuscular DiseasesNuclearNuclear ExportNuclear ImportNuclear ProteinNutrientOrganellesOrganismOuter Mitochondrial MembranePathway interactionsPremature BirthProcessProtein BiosynthesisProteinsProteomeQuality ControlRNARNA ProcessingRNA SplicingRegulationResearchResearch Project SummariesReverse TranscriptionRoleSaccharomycetalesSignal TransductionSiteStressSurfaceTestingTransfer RNAYeast Model SystemYeastsendonucleaseexperimental studygene productgenome wide screenin vivomitochondrial membranenovelnucleasepiRNApreventprogramsprotein degradationrepairedresponsetRNA Precursortooltrafficking
项目摘要
Project Summary
This research program focuses on tRNA biosynthesis and its subcellular trafficking. In addition to their
essential role in protein synthesis, tRNAs are required for nutrient signaling, regulation of apoptosis, protein
degradation, and priming retroviral reverse transcription. tRNA biogenesis requires a complex set of conserved
gene products for post-transcriptional processing and subcellular traffic. 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. tRNA dynamics consist of 3 steps: “primary export” of tRNA from the nucleus to the
cytoplasm, “retrograde nuclear import” of cytoplasmic tRNA into the nucleus, and “re-export” of the imported
tRNAs back to the cytoplasm. The mechanisms by which tRNAs move between the nucleus and the cytoplasm
are not completely understood. Because tRNA nuclear export is essential and the known exporters are
unessential, we conducted an unbiased genome-wide screen in yeast to search for the missing tRNA nuclear
exporter(s). We discovered that mutations of two pathways utilized for protein (Crm1) and mRNA (Mex67-Mtr2)
nuclear export also cause defective tRNA nuclear export; the data support the model that Crm1 and Mex67-
Mtr2 function in tRNA nuclear export. Aim 1 employs in vivo biochemical analyses to test the hypothesis that
tRNAs directly interact with the Crm1 and/or Mex67-Mtr2 nuclear export machinery and to learn how these
alternative nuclear export pathways recognize tRNA substrates. Aim 1 also seeks to test whether a candidate
tRNA nuclear importer physically interacts with tRNA. Aim 2 addresses the biological function for tRNA bi-
directional traffic between the nucleus and cytoplasm. We discovered that one function is for tRNA quality
control that prevents aberrant tRNA from interacting with the protein synthesis machinery. Aberrant tRNAs
reach the cytoplasm, in part, due to error-prone nuclear export. We will analyze the fidelity of the parallel tRNA
nuclear export pathways and determine whether aberrant tRNAs are corrected and/or destroyed upon
retrograde import into the nucleus. Aim 3 addresses RNA processing steps that occur on the mitochondrial
membrane. Pre-tRNA splicing in yeast and piRNA processing in metazoans occur on the mitochondrial
surface. We identified proteins that likely function in directing the tRNA splicing endonuclease and/or tRNAs to
mitochondria and we propose to test these roles. The information gained should inform how and why the
mitochondrial surface functions as a “warehouse” for RNA processing. 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)
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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:
10473791 - 财政年份:2017
- 资助金额:
$ 32.76万 - 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:
$ 32.76万 - 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:
$ 32.76万 - 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:
$ 32.76万 - 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:
$ 32.76万 - 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:
$ 32.76万 - 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:
$ 32.76万 - 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:
$ 32.76万 - 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:
$ 32.76万 - 项目类别:
YEAST GENES IN RNA PROCESSING & NUCLEUS/CYTOSOL EXCHANGE
RNA 加工中的酵母基因
- 批准号:
6018518 - 财政年份:1979
- 资助金额:
$ 32.76万 - 项目类别:
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