The Role of Edc3 in Drosophila Melanogaster Neuronal Development

<p>Enhancer of mRNA-decay 3 (Edc3) is a component of multiple decapping complexes that regulates the transcriptome by targeting a subset of transcripts for decapping for 5’-to-3’ messenger RNA (mRNA) decay. A missense mutation in the conserved Lsm domain of Edc3 has been reported in two siblings presenting with mild, non-syndromic intellectual disability (ID), however, the role of Edc3 is neuronal development has never been evaluated. Here, we use the <em>Drosophila melanogaster</em> model system to investigate the effects of Edc3 disruption on neuronal development. We found Edc3 reduction leads to significant hyperplasia at the larval neuromuscular junction (NMJ), providing the first evidence of a synaptic phenotype of Edc3 in any model system. To better understand how Edc3 regulates neurite morphogenesis in <em>Drosophila</em>, we performed RNA-sequencing and identified a subset of neuronal transcripts differentially stabilized when Edc3 is disrupted, with the bulk of genes downregulated. We performed a genetic interaction NMJ screen and identified several candidate genes predicted to be targets of Edc3 for decapping and 5’-to-3’ mRNA decay to regulate neurite morphogenesis. Additionally, we found several targets that interact genetically with Edc3 that are downregulated when Edc3 expression is reduced, suggesting Edc3 may target these transcripts to regulate neurite morphogenesis independently of the 5’-to-3’ mRNA decay pathway.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Year dc:date.available

2024

Author dc:creator

• Zius, Keelan

Contributors dc:contributor

• Scott A. Barbee
• Yan Qin
• Eugenia Olesnicky
• Daniel Linseman

• Drosophila melanogaster
• mRNA
• Enhancer of mRNA-decay 3 (Edc3)
• Biochemistry, Biophysics, and Structural Biology
• Cell and Developmental Biology
• Cell Biology
• Developmental Biology
• Life Sciences
• Molecular Biology

Statement dc:rights

• <p>Copyright is held by the author. User is responsible for all copyright compliance.</p>

Language dc:language

English (eng)

Repository record dc:identifier

https://digitalcommons.du.edu/etd/2408

OAI identifier oai:identifier

oai:digitalcommons.du.edu:etd-3402