Publicação
The interplay between nonsense-mediated mRNA decay and DIS3L2
| dc.contributor.advisor | Clarke,Luka Alexander | |
| dc.contributor.advisor | Santos,Rafaela Lacerda | |
| dc.contributor.author | Calado,Catarina Nunes | |
| dc.contributor.institution | Faculty of Sciences | |
| dc.contributor.institution | Department of Plant Biology | |
| dc.date.accessioned | 2026-05-26T08:25:08Z | |
| dc.date.available | 2026-05-26T08:25:08Z | |
| dc.date.issued | 2025 | |
| dc.description | Tese de mestrado, Biologia Molecular e Genética, 2025, Universidade de Lisboa, Faculdade de Ciências | |
| dc.description.abstract | Nonsense-mediated mRNA decay (NMD) is a translational-dependent quality control pathway that targets mRNA containing a premature termination codon (PTC) to degradation. Nevertheless, NMD also degrades natural targets, working as an expression regulator in the cell. Recently studies have proven the involvement of Defective in sister chromatin joining like 3´-5´desoxyribonuclease 2 (DIS3L2) in NMD. Despite NMD being involved in several regulations in eukaryotic cells, its regulatory mechanisms are still poorly understood. Previous work done in our laboratory indicates transcripts’ 3´ untranslated regions (UTR) may be influencing DIS3L2 target specificity, and that a high GC region in the 3´UTR of the NMD natural target, growth arrest and DNA damage inducible A (GADD45A), could be the cause of this specificity. With this work, we aim to verify if mRNA’s 3´UTR is implicated in DIS3L2 target specificity and if 3´UTR mRNA GC content is involved in that specificity. We proceed with a cloning strategy using constructs with fragments of GADD45A, and HBB, which is a well-known NMD-resistant gene. Our experimental results show evidence that mRNA GC content is an mRNA feature sufficient to activate NMD but not specific DIS3L2 degradation. We also aim to understand how mRNA circularization contributes to mRNA degradation by DIS3L2. We initiated a PABPC inhibitory protein - Poly(A)-binding protein interacting protein 2 (PAIP2)-knockdown assay. However, this experiment could not be concluded. We also aim to corroborate results of previous work done in our laboratory, which analysed the NMD involved proteins, up-frameshift protein 2 (UPF2) and RNA binding protein with serine-rich domain 1 (RNPS1), association with DIS3L2. Our experiments show that DIS3L2 and UPF2 may act together in HERV-H LTR-associating 3 (HHLA3) degradation; however, our results are not robust enough to draw conclusions. With this work, we added more information about how NMD mechanism and DIS3L2 are implicated in mRNA degradation. | en |
| dc.format | application/pdf | |
| dc.identifier.tid | 204174236 | |
| dc.identifier.uri | http://hdl.handle.net/10400.5/118722 | |
| dc.language.iso | eng | |
| dc.subject | Nonsense-mediated mRNA decay | |
| dc.subject | DIS3L2 | |
| dc.subject | NMD mRNA features | |
| dc.subject | mRNA circularization | |
| dc.subject | mRNA GC content | |
| dc.title | The interplay between nonsense-mediated mRNA decay and DIS3L2 | en |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | embargoedAccess |
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