Matching Items (4)
Filtering by
- Creators: School of Life Sciences
- Creators: Coletta, Dawn
Description
microRNAs (miRNAs) are short ~22nt non-coding RNAs that regulate gene output at the post-transcriptional level. Via targeting of degenerate elements primarily in 3'untranslated regions (3'UTR) of mRNAs, miRNAs can target thousands of varying genes and suppress their protein translation. The precise mechanistic function and bio- logical role of miRNAs is not fully understood and yet it is a major contributor to a pleth- ora of diseases, including neurological disorders, muscular disorders, and cancer. Cer- tain model organisms are valuable in understanding the function of miRNA and there- fore fully understanding the biological significance of miRNA targeting. Here I report a mechanistic analysis of miRNA targeting in C. elegans, and a bioinformatic approach to aid in further investigation of miRNA targeted sequences. A few of the biologically significant mechanisms discussed in this thesis include alternative polyadenylation, RNA binding proteins, components of the miRNA recognition machinery, miRNA secondary structures, and their polymorphisms. This thesis also discusses a novel bioinformatic approach to studying miRNA biology, including computational miRNA target prediction software, and sequence complementarity. This thesis allows a better understanding of miRNA biology and presents an ideal strategy for approaching future research in miRNA targeting.
ContributorsWeigele, Dustin Keith (Author) / Mangone, Marco (Thesis director) / Katchman, Benjamin (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-12
Description
Stroke is a devastating disease that affects thousands of individuals each year. Stroke, specifically cerebral ischemia, and immune responses are important areas of study and focus. Previous studies on stroke in mouse models had shown the upregulation of a specific micro-RNA: miR-1224. We hypothesized that miR-1224 was responsible for the regulation of the ST2 receptor protein’s expression. We performed cellular transfection on murine splenocytes with four different miRNAs—miR-1224-mimic, miR-1224-inhibitor, miR-451-mimic, and a control. We predicted that transfection with 1224m would decrease ST2 expression, while transfection with 1224i would increase ST2 expression. Two complete trials were run, and analysis of the results included RT-PCR of both miRNA samples and mRNA samples to confirm transfection and controlled transcription. Reverse transcription and qPCR of miRNA was done in order to confirm that transfection was in fact successful. Reverse transcription and qPCR of the mRNA was done in order to confirm that ST2 mRNA was not altered; this allowed us to attribute any changes in ST2 protein levels to miRNA interactions, as the mRNA levels were consistent. Western blotting was done in order to assess relative protein content. We found that transfection with 1224m slightly decreased ST2 expression and transfection with 1224i slightly increased ST2 expression, however, after assessing the p-values through statistical analyses, neither difference was significant. As such, our hypothesis was rejected as it is not evident that miR-1224 plays a significant role on ST2 gene expression. Future studies are needed in order to analyze alternate protein targets to fully assess the role of miR-1224.
ContributorsReddy, Nihaal (Author) / Holechek, Susan (Thesis director) / Ahmad, Saif (Committee member) / Wood, Kristofer (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Obesity and related health disparities including type 2 diabetes disproportionately impact Latino youth. These health disparities may be the result of gene-environment interactions, but limited research has examined these interactions in the pediatric age group. Lifestyle intervention is the cornerstone for preventing diabetes among high-risk populations and epigenetic and genetic factors may help explain the biological mechanisms underlying diabetes risk reduction following lifestyle changes. MicroRNAs (miRNAs) are small, non-coding RNA’s that regulate gene expression and have emerged as potential biomarkers for predicting type 2 diabetes risk in adults but have yet to be applied to youth. Therefore, the purpose of this study was to identify changes in miRNA expression among Latino youth with prediabetes (4 female/2 male, ages 14-16, BMI percentile 99 ±.2) who participated in a 12-week lifestyle intervention focused on increasing physical activity and improving nutrition-related behaviors.
ContributorsKarch, Jamie (Co-author) / Day, Samantha (Co-author) / Shaibi, Gabriel (Thesis director) / Coletta, Dawn (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The Numb gene encodes an adaptor protein that has been shown to play a role in muscle repair, cell proliferation, and the determination of cell fate in satellite cells. Ablation of this gene in satellite cells results in an up-regulation of myostatin and p21, which inhibit the proliferation of myoblasts. These results indicate that the regulation of numb and myostatin could be used to amplify muscle regeneration. This would function as a therapeutic approach to degenerative muscle diseases, such as muscular dystrophy. There are four mammalian NUMB proteins produced through alternative splicing of the Numb mRNA transcript. Only two isoforms are present in adult mammalian muscle, indicating some form of muscle-specific post-transcriptional control of the gene. Additionally, the presence of two polyadenylation sites, and multiple miRNA seed sequences within the 3’ untranslated region (UTR) of mouse Numb indicate the possibility of regulation by a muscle specific miRNA.
ContributorsGefroh, Bailey Emelia (Co-author) / Gefroh, Bailey (Co-author) / Wilson-Rawls, Jeanne (Thesis director) / Rawls, Alan (Committee member) / Palade, Joanna (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12