A Neuroprotective Role for Mir-1017, a Non-Canonical Mirna

<p>miRNAs are post-transcriptional regulators of gene expression, with numerous being involved in neurobiology. Within the human genome a quarter of the identified miRNA loci derive from a class of miRNAs termed tailed mirtrons. Despite the identification of this large population of miRNA, no functional studies have been conducted to identify their role. In this study we examined the highly expressed and deeply conserved Drosophila 3’ tail mirtron, miR-1017, as a candidate to elucidate tailed mirtron functionality. We identified acetylcholine receptor transcripts, Da5 and Da2, as bona fide targets for miR-1017. Interestingly, Da2 is also the host transcript for miR-1017. We utilized the GAL4/UAS system, to observe the miR-1017 expression pattern; furthermore we witnessed a disrupted feedback loop in the miR-1017 null background resulting in higher Da2 transcriptional activation. This could be phenocopied with the acetylcholine receptor (AchR) activity antagonist, Donepezil, which likewise resulted in higher GFP expression. Together this suggests that Da2 transcription is modulated by acetylcholine neurotransmission. Consistent with a role in dampening AchR activity miR-1017 mutant flies exhibit a neurodegeneration due to excitotoxicity. Ectopic expression of miR-1017 within an Alzhiemers disease fly model dampened the pathologenesis and improved neurological function and lifespan. Therefore revealing miR-1017, a 3’ tailed mirtron, as a significant neuroprotector within Drosophila. The coupled expression of Da2 and miR-1017 works as a negative feedback loop that limits activity dependent transcription of Da2.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Masters Thesis

Discipline thesis:degree_discipline

Biological Sciences

Year dc:date.available

2017

Author dc:creator

• de Cruz, Matthew

Contributors dc:contributor

• Alex Flynt
• Fengwei Bai
• Shahid Karim

• 3' Tailed mirtron
• Neuroprotective
• miR-1017
• Biotechnology
• Molecular and Cellular Neuroscience
• Molecular Genetics

Repository record dc:identifier

https://aquila.usm.edu/masters_theses/326

OAI identifier oai:identifier

oai:aquila.usm.edu:masters_theses-1364