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dc.contributor.advisorHunter, Craigen_US
dc.contributor.advisorKunes, Samen_US
dc.contributor.authorManiatis, Silas danaen_US
dc.date.accessioned2015-07-17T17:59:17Z
dc.date.created2015-05en_US
dc.date.issued2015-05-14en_US
dc.date.submitted2015en_US
dc.identifier.citationManiatis, Silas dana. 2015. Classical Conditioning Alters Short Noncoding RNA Expression in Drosophila. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17467392
dc.description.abstractMicroRNAs (miRNAs) and other classes of short non-coding RNAs regulate essential processes in the development and function of the nervous system. Regulation of miRNAs by neural activity has also been reported. Recently, instances of piwi interacting RNA (piRNA) and endogenous short interfering RNA (esiRNA) mediated modulation of neural physiology have been reported. To better understand the role of miRNAs and other classes of short non-coding RNAs in long term memory (LTM) formation, we have conducted high throughput sequencing on 15-35nt RNAs isolated from heads of Drosophila that have been subjected to aversive olfactory conditioning. We developed genome wide profiles of miRNA, piRNA, and esiRNA, and tested for differential expression following conditioning. We find that 5 miRNAs exhibit significant regulation in the conditioned group. We identify several esiRNA generating loci within genes required for olfactory LTM formation. Our data reveal that an intron of the multiple wing hairs (mwh) gene forms secondary structures and generates esiRNAs following conditioning from regions that correspond to lysozyme family genes located within the mwh intron. We find that piRNAs are produced in fly heads, and that a small set of piRNA generating loci mapping to LTR retrotransposons are significantly down regulated following conditioning. In addition to the well characterized classes of short non coding RNAs, we describe a set of transcripts that produce large numbers of reads with a broad size distribution from the sense strand. We find that a subset of these are regulated following treatment and contain consensus elements that may be involved in their regulation. We investigate expression of one such gene with dramatically up-regulated reads following treatment, the Drosophila beta-site APP-cleaving enzyme (dBACE), and find that increased reads reflect increased mRNA levels. Further, we find that the target of dBACE protein, drosophila β amyloid protein precursor-like (APPL), is subjected to increased cleavage following conditioning, and that dBACE is required for LTM formation, but not for learning or STM.en_US
dc.description.sponsorshipBiology, Molecular and Cellularen_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoenen_US
dash.licenseLAAen_US
dc.subjectBiology, Molecularen_US
dc.titleClassical Conditioning Alters Short Noncoding RNA Expression in Drosophilaen_US
dc.typeThesis or Dissertationen_US
dash.depositing.authorManiatis, Silas danaen_US
dc.date.available2015-07-17T17:59:17Z
thesis.degree.date2015en_US
thesis.degree.grantorGraduate School of Arts & Sciencesen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
dc.contributor.committeeMemberMurthy, Venkateshen_US
dc.contributor.committeeMemberSanes, Joshuaen_US
dc.type.materialtexten_US
thesis.degree.departmentBiology, Molecular and Cellularen_US
dash.identifier.vireohttp://etds.lib.harvard.edu/gsas/admin/view/372en_US
dc.description.keywordssRNA;miRNA;drosophila;memoryen_US
dash.author.emailsilasdmaniatis@gmail.comen_US
dash.identifier.drsurn-3:HUL.DRS.OBJECT:25164903en_US
dash.contributor.affiliatedManiatis, Silas dana


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