Role of an RNA granule in the jus-dependent mechanism of epileptogenesis in Drosophila
| dc.contributor.author | Anirudh Sharma | |
| dc.date.accessioned | 2024-05-24T17:57:20Z | |
| dc.date.available | 2024-05-24T17:57:20Z | |
| dc.date.issued | 2024-05-24 | |
| dc.description.abstract | This work aims to identify the role of an RNA granule in the development of epilepsy in Drosophila melanogaster. Prior studies have shown varying degrees of evidence of granule-associated macromolecules co-localizing with Jus, a previously-studied protein whose dysfunction during development is associated with a bang-sensitive phenotype that models human epilepsy. By assessing the bang-sensitivities (via vortex testing) of flies with altered expression of RNA-granule markers (via transposon-insertional mutation or GAL4-UAS driven RNA interference and overexpression), it was found that altered function of RNA granules is associated with the jus-dependent mechanism of epileptogenesis. In particular, the primary finding was that overexpression of the gene FMR1 (whose protein product contains numerous RNA-binding motifs) in jus-expressing neurons is associated with enhanced bang sensitivity in both wild-type flies and jus-mutant heterozygotes. Additional genetic crosses were conducted to support the finding that this effect was specific to jus-expressing neurons. However, western blot analyses show that Jus levels were not consistently altered in flies where FMR1 was overexpressed or knocked down, indicating that the role of the RNA granule in epileptogenesis needs closer examination and that FMR1 does not directly regulate jus expression. Additionally, a mutation of the gene CG31249, a known member of the RNA granule, was associated with enhanced bang sensitivity in jus-mutant heterozygotes and increased mean recovery times (an indication of seizure intensity) in jus-mutant homozygotes. Overall, this work provides multiple lines of evidence for the role of an RNA granule in causing seizures in Drosophila. | |
| dc.identifier.uri | https://hdl.handle.net/1813/115241 | |
| dc.language.iso | en | |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | seizures | |
| dc.subject | bang-sensitivity | |
| dc.subject | epilepsy | |
| dc.subject | julius seizure | |
| dc.subject | RNA granule | |
| dc.title | Role of an RNA granule in the jus-dependent mechanism of epileptogenesis in Drosophila | |
| dc.type | dissertation or thesis | |
| schema.accessibilityFeature | readingOrder |
Files
Original bundle
1 - 1 of 1