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dc.contributor.advisorVictor Ambros, PhD
dc.contributor.authorRen, Zhiji
dc.date2022-08-11T08:08:45.000
dc.date.accessioned2022-08-23T16:07:14Z
dc.date.available2022-08-23T16:07:14Z
dc.date.issued2016-02-26
dc.date.submitted2016-10-11
dc.identifier.doi10.13028/M22G6V
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32207
dc.description.abstractMicroRNAs (miRNAs) are endogenous non-coding small RNAs that posttranscriptionally regulate gene expression primarily through binding to the 3’ untranslated region (3’UTR) of target mRNAs, and are known to play important roles in various developmental and physiological processes. The work presented in this thesis was centered on understanding how Caenorhabditis elegans miRNAs are modulated by genetic, environmental, or physiological factors and how these small RNAs function to maintain the robustness of developmental processes under stressful conditions. To identify modulators of the miRNA pathway, I developed sensitized genetic backgrounds that consist of a panel of miRNA gene mutants and miRNA biogenesis factor mutants with partially penetrant phenotypes. First, I found that upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an opportunistic pathogen of diverse plants and animals, let-7 family miRNAs are engaged in reciprocal regulatory interactions with the p38 MAPK innate immune pathway to maintain robust developmental timing despite the stress of pathogen infection. These let-7 family miRNAs, along with other developmental timing regulators, are also integrated into innate immune regulatory networks to modulate immune responses. Next, I demonstrated that loss-of-function mutations of Staufen (stau-1), a double-stranded RNA-binding protein, increase miRNA activity for several miRNA families, and this negative modulation of Staufen on miRNA activity acts downstream of miRNA biogenesis, possibly by competing with miRNAs for binding to target mRNA 3’UTRs. In summary, these studies provide a better understanding on how miRNAs are modulated by various environmental and cellular components, and further support the role of the miRNA pathway in conferring robustness to developmental processes under these perturbations.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectDissertations, UMMS
dc.subjectCaenorhabditis Elegans
dc.subjectMicroRNAs
dc.subject3' Untranslated Regions
dc.subjectRNA-Binding Proteins
dc.subjectRNA Interference
dc.subjectCaenorhabditis elegans Proteins
dc.subjectCaenorhabditis Elegans
dc.subjectMicroRNAs
dc.subject3' Untranslated Regions
dc.subjectRNA-Binding Proteins
dc.subjectRNA Interference
dc.subjectCaenorhabditis elegans Proteins
dc.subjectDevelopmental Biology
dc.titleIdentification and Characterization of MicroRNA Modulators in Caenorhabditis Elegans: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1837&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/835
dc.legacy.embargo2017-03-08T00:00:00-08:00
dc.identifier.contextkey9254413
refterms.dateFOA2022-08-26T03:17:25Z
html.description.abstract<p>MicroRNAs (miRNAs) are endogenous non-coding small RNAs that posttranscriptionally regulate gene expression primarily through binding to the 3’ untranslated region (3’UTR) of target mRNAs, and are known to play important roles in various developmental and physiological processes. The work presented in this thesis was centered on understanding how Caenorhabditis elegans miRNAs are modulated by genetic, environmental, or physiological factors and how these small RNAs function to maintain the robustness of developmental processes under stressful conditions.</p> <p>To identify modulators of the miRNA pathway, I developed sensitized genetic backgrounds that consist of a panel of miRNA gene mutants and miRNA biogenesis factor mutants with partially penetrant phenotypes. First, I found that upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an opportunistic pathogen of diverse plants and animals, let-7 family miRNAs are engaged in reciprocal regulatory interactions with the p38 MAPK innate immune pathway to maintain robust developmental timing despite the stress of pathogen infection. These let-7 family miRNAs, along with other developmental timing regulators, are also integrated into innate immune regulatory networks to modulate immune responses. Next, I demonstrated that loss-of-function mutations of Staufen (stau-1), a double-stranded RNA-binding protein, increase miRNA activity for several miRNA families, and this negative modulation of Staufen on miRNA activity acts downstream of miRNA biogenesis, possibly by competing with miRNAs for binding to target mRNA 3’UTRs.</p> <p>In summary, these studies provide a better understanding on how miRNAs are modulated by various environmental and cellular components, and further support the role of the miRNA pathway in conferring robustness to developmental processes under these perturbations.</p>
dc.identifier.submissionpathgsbs_diss/835
dc.contributor.departmentProgram in Molecular Medicine
dc.description.thesisprogramInterdisciplinary Graduate Program


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