In eukaryotes, the initiation phase of protein synthesis or translation is a multi-step process that culminates in the positioning of the SOS ribosome at the initiation codon of a messenger RNA (mRNA). Recognition of the cap structure by eukaryotic initiation factor 4F (etF4F; composed of three subunits: the cap-binding protein e1F4E, the RNA-helicase eIF4A and the scaffolding protein eIF4G) facilitates this process. The ability of eIF4F to bind to the cap, as a result of the Cap:eIF4E interaction is of particular importance, as it is the major target of translational regulatory mechanism. / Early embryogenesis requires the activity of various maternal determinants called morphogens, whose spatial and temporal expressions are tightly regulated at the level of translation. Positional information encoded within these factors is thus important for the establishment of body polarity. For instance, in Drosophila, when maternal Caudal (Cad) and Hunchback (Hb) proteins are allowed to accumulate inappropriately in an embryo, anterior and abdominal segmentations are blocked. Hence, the precision of Cad and Hb expression domains is critical for normal development. / An eIF4E-related protein called eIF4E-Homologous protein (4EHP) was first described in 1998. However, the function, if any, of 4EHP in translation has been elusive, since it does not interact with any known initiation factors. In order to elucidate its biological function, the power of Drosophila genetics was used. In this thesis, I show that the Drosophila homolog of 4EHP (d4EHP) interacts with Bicoid (Bcd) and Brain tumor (Brat) proteins to inhibit the translation of maternal cad and hb mRNAs. Simultaneous interaction of d4EHP with the cap and Bcd or Brat results in mRNA circularization, which renders cad and hb mRNAs translationally inactive. This example of cap-dependent translational control that is not mediated by eIF4E defines a new paradigm for translational inhibition involving tethering of the mRNA 5' and 3' ends.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.111819 |
| Date | January 2005 |
| Creators | Cho, Park, 1975- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002329633, proquestno: AAINR25117, Theses scanned by UMI/ProQuest. |
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