tRNA editing by deamination: Balancing affinity and specificity
tRNA editing by deamination: Balancing affinity and specificity
批准号:
9767224
负责人:
Juan D Alfonzo
金额:
$36.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-08-01 至 2022-05-31
关键词:
AddressAffinityAnticodonBackBiochemicalBiologicalBiological AssayBiologyCapsicumCell NucleusCellular biologyChemicalsCodon NucleotidesDNADeaminaseDeaminationDefectDeuteriumEnsureEnzymesEquilibriumEventEvolutionGene ExpressionGenesGenetic TranscriptionGenomeGenomicsHumanImmunoglobulin GImmunoglobulin Somatic HypermutationIn VitroIsotope LabelingLeadLeishmaniaLuciferasesMapsMass Spectrum AnalysisMedicalMessenger RNAMethylationMethyltransferaseModificationMolecularMutagenesisNucleic AcidsNucleotidesOrganismOutcomePathway interactionsPlayPositioning AttributeProtein BiosynthesisProteinsRNARNA EditingRNA InterferenceReactionRecombinantsResearchRestRibosomal RNARoleSeriesSignal TransductionSiteSmall Nuclear RNASpecific qualifier valueSpecificityStructural ModelsStructureSystemTechniquesTherapeutic InterventionTransfer RNATranslationsTrypanosomaTrypanosoma brucei bruceiUncertaintyactivation-induced cytidine deaminasebasebiophysical techniquescrosslinkenzyme mechanismepigenetic regulationhuman diseasein vitro Assayin vivointerestmemberpathogenprotein protein interactionribosome profilingtandem mass spectrometrytargeted treatment
中文摘要
在所有生物体中,trna通过一系列转录后加工成熟
英文摘要
In all organisms, tRNAs are matured by a series of post-transcriptional processing
events before they can partake in protein synthesis. These include end trimming to
generate the correct 5' and 3' ends, and a substantial number of post-transcriptional
chemical modifications; these ensure proper structure and function. Despite much effort
many modifications have not been recapitulated in vitro, which have made
understanding their mechanism difficult, if not impossible. One such event entails the C
to U editing of tRNAs at the anticodon, a discovery that dates back to almost 25 years,
but one for which no in vitro assay was available. Recently, we established the first in
vitro assay for C to U editing in any system. Our studies also revealed that before editing
can take place, the edited position must also be methylated and both enzymes, the
deaminase and the methylase, strictly require each other for activity. This allowed us to
introduce a new concept of “enzyme co-activation”, one that may guide biochemical
studies of other modifications for which no in vitro assay currently exist. Additionally,
given that tRNA editing and modification in T. brucei is peppered with unique features,
successful completion of these studies will generate important basic information on the
mechanism and evolution of tRNA editing and modification, reveal unique features
specific to T. brucei but which undoubtedly impact other systems.
!
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