RIBOSOME IN THE BALANCE: STRUCTURAL EQUILIBRIUM ENSURES TRANSLATIONAL FIDELITY AND PROPER GENE EXPRESSION

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dc.contributor.advisorDinman, Jonathan Den_US
dc.contributor.authorMusalgaonkar, Sharmishthaen_US
dc.contributor.departmentCell Biology & Molecular Geneticsen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2015-02-06T06:35:15Z
dc.date.available2015-02-06T06:35:15Z
dc.date.issued2014en_US
dc.description.abstractAt equilibrium, empty ribosomes freely transit between the rotated and un-rotated states. In translation elongation, the binding of two translation elongation factors to the same general region of the ribosome stabilizes them in one of the two extremes of intersubunit rotation; rotated or unrotated. These stabilized states are resolved by expenditure energy in the form of GTP hydrolysis. Here, mutants of the early assembling integral ribosomal protein uL2 (universal L2) are used to test the generality of this hypothesis. A prior study employing mutants of a late assembling peripheral ribosomal protein suggested that ribosome rotational status determines its affinity for elongation factors, and hence translational fidelity and gene expression. rRNA structure probing analyses reveal that mutations in the uL2 B7b bridge region shift the equilibrium towards the rotated state, propagating rRNA structural changes to all of the functional centers of ribosome. Shift in structural equilibrium affects the biochemical properties of ribosomes: rotated ribosomes favor binding of the eEF2 translocase and disfavor that of the elongation ternary complex. This manifests as specific translational fidelity defects, impacting the expression of genes involved in telomere maintenance. A model is presented here describing how cyclic intersubunit rotation ensures the unidirectionality of translational elongation, and how perturbation of rotational equilibrium affects specific aspects of translational fidelity and cellular gene expression.en_US
dc.identifierhttps://doi.org/10.13016/M2QS4M
dc.identifier.urihttp://hdl.handle.net/1903/16155
dc.language.isoenen_US
dc.subject.pqcontrolledBiologyen_US
dc.subject.pqcontrolledMolecular biologyen_US
dc.subject.pqcontrolledCellular biologyen_US
dc.subject.pquncontrolledgene expressionen_US
dc.subject.pquncontrolledriboomal proteinsen_US
dc.subject.pquncontrolledRibosomesen_US
dc.subject.pquncontrolledribosomopathiesen_US
dc.subject.pquncontrolledrotational equilibriumen_US
dc.subject.pquncontrolledtranslation fidelityen_US
dc.titleRIBOSOME IN THE BALANCE: STRUCTURAL EQUILIBRIUM ENSURES TRANSLATIONAL FIDELITY AND PROPER GENE EXPRESSIONen_US
dc.typeDissertationen_US

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