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Uniform TitleBrain-specific microRNAs induce neurogenesis through indirect regulation of Mef2C activity
NameGoff, Loyal Andrew (author), Hart, Ronald (chair), Padgett, Richard (internal member), Grumet, Martin (internal member), Jornsten, Rebecka (internal member), Getts, Robert (outside member), Rutgers University, Graduate School - New Brunswick,
Degree Date2008-05
Date Created2008
SubjectCell and Developmental Biology,
Non-coding RNA,
Developmental neurobiology
DescriptionMicroRNAs represent a group of functional non-coding RNAs (ncRNA) with a role in both translational repression and/or RNAi-mediated degradation of specific target mRNAs. Reports indicate that microRNA regulation plays an important role in numerous cellular processes. We have identified microRNAs regulated during induction of neurogenesis in an in vitro model, and have correlated the expression of these specific microRNAs to regulated mRNAs with the goal of describing potential functional interactions between the two sets of molecules. We demonstrate the active role these regulated microRNAs play in inducing a neuronal phenotype in uncommitted neural precursor cells. As a result of this analysis, as well as additional studies of regulated mRNA transcripts during neurogenesis, we have identified a regulated transcription factor, Mef2C, which is chromosomally adjacent to one of the regulated microRNAs. The unexpected appearance of this transcription factor and its relatively unexplored role in neural differentiation suggest that Mef2C may play a role in this cellular process. This single genomic locus containing an induced microRNA involved in neuronal fate determination, as well as Mef2C, is transcriptionally regulated during neuronal cell specification. In addition, HDAC4, a known repressor of Mef2C activity is validated as a target for miR-9 mediated post-transcriptional repression. Described here is a putative network of interactions that arise from transcriptional activation of this locus, with the end result contributing to the induction of a neuronal phenotype.
NotePh.D.
NoteIncludes bibliographical references (p. 96-110).
Genretheses
Persistent URLhttp://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17318
LanguageEnglish
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.