Discovery of Independent Suppressors in C. elegans During CMTR1 Knockdown: Insights from a Generic Screen
| dc.contributor.advisor | Pettitt, Jonathan | |
| dc.contributor.author | Alotaibi, Omar | |
| dc.date.accessioned | 2024-12-13T09:55:26Z | |
| dc.date.issued | 2024 | |
| dc.description | This research explores the biological regulation and functional importance of CMTR1, a key enzyme involved in 2'-O-ribose methylation, a chemical modification of RNA. Using C. elegans as a model organism, the study employs a mutagenesis approach to uncover genetic suppressors that can compensate for the loss of CMTR1 function and restore fertility. The findings provide insights into the complex regulatory networks involving CMTR1 and its role in cellular processes. This work enhances our understanding of the broader biological implications of RNA modifications, particularly their critical role in maintaining fertility and overall organismal health. | |
| dc.description.abstract | In this study, we used C. elegans as a model organism to investigate the regulation and function of CMTR1 through a direct mutagenesis screen using ethyl methanesulfonate (EMS). Our goal was to identify suppressors of CMTR1 knockdown that could restore fertility, employing an auxin-inducible degradation (AID) system to target CMTR1. However, we anticipated that EMS mutagenesis would reveal faults in the AID system, particularly through TIR1 loss-of-function mutations, which inadvertently prevented CMTR1 degradation and allowed the variants to maintain fertility. Our results confirmed our hypothesis, showing that TIR1 loss-of-function mutations prevent the degradation of CMTR1, thereby allowing CMTR1 to persist and the variants to maintain fertility. Analysing the frequency and nature of these mutations will be essential for estimating the size of the genuine suppressor targets identified through EMS screening. This approach will help us gauge the extent and scope of the suppressors that can compensate for CMTR1 knockdown. In addition to these control-related findings, we successfully identified Suppressors of CMTR1 Knockdown (SOCK) that restored fertility through mutations in other proteins or regulatory sequences. These findings suggest a complex regulatory network involving CMTR1, highlighting its crucial function beyond immune recognition and opening new avenues for understanding the broader biological roles of 2'-O-ribose methylation. In conclusion, this research can provide a clearer understanding of the importance of cap 1 and 2'-O-ribose methylation in cellular activities, highlighting their crucial roles in preserving fertility | |
| dc.format.extent | 25 | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14154/74168 | |
| dc.language.iso | en | |
| dc.publisher | University of Aberdeen | |
| dc.subject | C. elegans CMTR1 Mutagenesis Ethyl methanesulfonate (EMS) Auxin-inducible degradation (AID) TIR1 Loss-of-function Suppressors of CMTR1 Knockdown (SOCK) Fertility 2'-O-ribose methylation Cap 1 Immune recognition Regulatory network | |
| dc.title | Discovery of Independent Suppressors in C. elegans During CMTR1 Knockdown: Insights from a Generic Screen | |
| dc.type | Thesis | |
| sdl.degree.department | School of Medicine, Medical Sciences and Nutrition | |
| sdl.degree.discipline | Genetics | |
| sdl.degree.grantor | University of Aberdeen | |
| sdl.degree.name | Molecular Medicine |