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dc.contributor.advisorGregory, Richard Ian
dc.contributor.authorThornton, James Edward
dc.date.accessioned2013-10-18T14:02:16Z
dash.embargo.terms2015-10-10en_US
dash.embargo.terms2015-10-10
dc.date.issued2013-10-18
dc.date.submitted2013
dc.identifier.citationThornton, James Edward. 2013. Roles for Terminal Uridyl Transferases in the Post-Transcriptional Regulation of Developmental miRNAs. Doctoral dissertation, Harvard University.en_US
dc.identifier.otherhttp://dissertations.umi.com/gsas.harvard:11195en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11181173
dc.description.abstractMicroRNAs (miRNAs) are a diverse and evolutionarily conserved class of non-coding RNAs that play a multitude of roles in many branches of eukaryotic biology. The regulation of miRNAs is dynamically controlled both spatially and temporally, and the expression of miRNAs can be modulated at the level of transcription or at points downstream of the miRNA maturation process. A relevant example of post-transcriptional miRNA regulation is the blockade of let-7 precursor miRNAs by Lin28 in embryonic stem cells. This pathway, which is initiated by the small RNA-binding protein Lin28, recruits the terminal uridyl transferase (TUTase) Zcchc11 to add a non-templated oligouridine tail to the miRNAs 3' end, and signals it for degradation by the cytoplasmic exonuclease Dis3l2. The Lin28/let-7 axis is essential for development and metabolic homeostasis, and is reactivated in a subset of human cancers. This thesis describes the biochemical mechanism underlying Lin28-mediated degradation of let-7, as well as a novel role for Zcchc11 and the related TUTase Zcchc6 in targeting mature developmental miRNAs in a Lin28-independent manner.en_US
dc.language.isoen_USen_US
dash.licenseLAA
dc.subjectBiochemistryen_US
dc.subjectMolecular biologyen_US
dc.subjectDevelopmental biologyen_US
dc.subjectlet-7en_US
dc.subjectmiRNAen_US
dc.subjectTUT4en_US
dc.subjectTUT7en_US
dc.subjectTUTaseen_US
dc.subjectUridylationen_US
dc.titleRoles for Terminal Uridyl Transferases in the Post-Transcriptional Regulation of Developmental miRNAsen_US
dc.typeThesis or Dissertationen_US
dash.depositing.authorThornton, James Edward
dc.date.available2015-10-10T07:33:03Z
thesis.degree.date2013en_US
thesis.degree.disciplineBiological Sciences in Public Healthen_US
thesis.degree.grantorHarvard Universityen_US
thesis.degree.leveldoctoralen_US
thesis.degree.namePh.D.en_US
dc.contributor.committeeMemberWessling-Resnick, Marianneen_US
dc.contributor.committeeMemberDaley, Georgeen_US
dc.contributor.committeeMemberLu, Quanen_US
dc.contributor.committeeMemberYuan, Zhi-Minen_US
dc.contributor.committeeMemberBuratowski, Steveen_US
dc.contributor.committeeMemberStruhl, Kevinen_US
dc.contributor.committeeMemberHorng, Tiffanyen_US
dash.contributor.affiliatedThornton, James Edward


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