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dc.contributor.authorBennett, Alexisen_US
dc.date.accessioned2016-07-06T17:31:32Z
dc.date.available2016-07-06T17:31:32Z
dc.date.issued2016
dc.identifier.urihttps://hdl.handle.net/2144/16799
dc.description.abstractRNA helicases are enzymes that bind or remodel RNA and RNA-protein complexes. They are involved in numerous cellular functions including RNA metabolism, transcription, translation, and mRNA decay. Defects in helicase function or disregulated expression, can cause diseases. DEAD-box (DDX) RNA helicases are highly conserved and are known to be involved in muscle development and disease, by interacting with muscle specific transcription factors and genes in humans. The Gupta Lab is currently studying zebrafish (an established and reliable model to study muscle diseases) with a mutation in ddx27. These fish have impaired motility behavior, skeletal muscle hypotrophy, and extensive central nucleation. They also exhibit disorganization of skeletal muscle, abnormalities in the brain, eyes, and heart. These phenotypes mimic the abnormalities seen in human myotonic dystrophy. It is known that ddx27 is necessary for regulation of rRNA maturation. Recent studies have pointed to it’s non-ribosomal roles of nucleolar genes. IGHMBP2, another RNA helicase, is known to result in spinal muscular atrophy (SMARD1) or Charcot-Marie Tooth disease when mutated. We used zebrafish and patient myoblast cells to determine the role of ddx27 in myogenesis and diseases. As a basis for future studies, the 43 known human DDX genes were outlined for their functions. Immunofluorescence studies in ddx27 mutant zebrafish showed drastic skeletal muscle and nucleolar assembly defects with large numbers of cells with transcriptionally active euchromatin, suggesting altered gene regulation. In addition, IF with Pax7 (a marker for satellite cells) and MF20 (a marker for myosin heavy chain antibodies) showed a significant increase in the number of Pax7 positive cells that suggest perturbed satellite cell regulation. Nucleolar defects were also seen in cells isolated from myotonic dystrophy patients. While the cause of these defects is not known, the results lead us to believe that ddx27 may be involved in cell cycle regulation or apoptosis events. Finally, while this study also attempted to develop a zebrafish model of IGHMBP2 deficiency in order to study and develop therapies for SMARD1, a consistent phenotype was not observed and further work is required to characterize this model. More than one million Americans suffer from neuromuscular disorders, however many of these conditions have no known treatments. By studying the molecular pathways involved we can attempt to develop therapies for these diseases.en_US
dc.language.isoen_US
dc.rightsAttribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGeneticsen_US
dc.titleThe role of RNA helicases in neuromuscular development and diseasesen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2016-06-17T19:41:45Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International