Please use this identifier to cite or link to this item:
http://arks.princeton.edu/ark:/88435/dsp01fb494c56g
Title: | Probing Translational Control during Drosophila Oogenesis: from nanos to the Entire Maternal Transcriptome |
Authors: | Peng, Yingshi |
Advisors: | Gavis, Elizabeth R |
Contributors: | Molecular Biology Department |
Keywords: | Fragile X mental retardation protein (FMRP) Glorund nanos Post-transcriptional gene regulation Translation elongation regulation Translational control |
Subjects: | Molecular biology Biochemistry Bioinformatics |
Issue Date: | 2021 |
Publisher: | Princeton, NJ : Princeton University |
Abstract: | Translational control provides a key mechanism for the spatial and temporal regulation of eukaryotic gene expression. It plays a particularly important role in early embryonic development in organisms that rely heavily on maternally supplied mRNAs. The Drosophila developing oocyte serves as a valuable model for studying translational control. The Drosophila posterior determinant, nanos (nos), is translationally repressed throughout the oocyte cytoplasm except at the posterior pole. A multi-functional RNA-binding protein Glorund (Glo), the homolog of the mammalian hnRNP F/H family of proteins, represses translation of nos during oogenesis by targeting both translation initiation and translation elongation. To elucidate the molecular mechanism by which Glo regulates nos, I identified dFMRP as a Glo-interacting protein. By biochemically dissecting repression of nos translation in vitro, I demonstrated that dFMRP specifically inhibits translation elongation. Furthermore, I combined mutational analysis and in vivo and in vitro binding assays to show that Glo’s qRRM2 domain specifically and directly interacts with dFMRP, suggesting that Glo’s RNA-binding domains can also function as protein-protein interaction interfaces critical for its regulatory functions. Additionally, I applied ribosome footprint profiling to the Drosophila ovary at different developmental stages to identify maternal transcripts regulated during the translation elongation phase. A footprint peak-finding tool has been developed to detect transcriptome-wide ribosome stalling sites. My preliminary results suggest that developmentally regulated ribosome stalling sites may be widely present on Drosophila maternal transcripts. An A-/P-site mapping algorithm is currently under development to facilitate mechanistic analysis of ribosome stalling during oogenesis. |
URI: | http://arks.princeton.edu/ark:/88435/dsp01fb494c56g |
Alternate format: | The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog: catalog.princeton.edu |
Type of Material: | Academic dissertations (Ph.D.) |
Language: | en |
Appears in Collections: | Molecular Biology |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Peng_princeton_0181D_13896.pdf | 3.39 MB | Adobe PDF | View/Download |
Items in Dataspace are protected by copyright, with all rights reserved, unless otherwise indicated.