Analysis of Factors Required for Centrocortin mRNA Localization to Centrosomes in Drosophila Embryos Público
Husbands, Christian (Summer 2023)
Abstract
Centrosomes are highly organized and dynamic organelles that serve as the primary microtubule organizing center in animal cells, playing a key role in ensuring proper cell division. Within centrosomes, a compartmentalized matrix of protein and RNA, known as the pericentriolar material (PCM), surrounds a pair of centrioles. Centrosomes function in a multitude of roles throughout the cell cycle, including intracellular trafficking, spindle assembly, and polarization. Recent work from our group demonstrates mRNA localizes to the PCM and contributes to centrosome function, raising the possibility of post-transcriptional links between centrosome dysfunction and disease. One of these centrosomal localizing mRNAs within syncytial Drosophila embryos, Centrocortin (cen), is significantly enriched at the centrosome, where it is organized into micron-scale ribonucleoprotein (RNP) granules. Moreover, cen mRNA mislocalization disrupts microtubule organization, leading to impaired nuclear division, increased nuclear fallout, and embryonic lethality. While local cen mRNA is required for centrosome function, precisely how cen mRNA is targeted to centrosomes remains incompletely understood. Thus, we are investigating the contribution of the minus-end directed dynein motor complex and associated regulatory cofactors to cen mRNA localization to centrosomes. We additionally reason that one or more specific sequences within the cen gene are responsible for localization. Prior work, for example, suggests cen translation is required for cen mRNA localization to centrosomes, given that cen mRNA and cen protein colocalize within cen RNPs at the centrosome and cen mRNA localization is impaired upon translation inhibition. We are investigating this model and identifying cis-elements within the cen coding region important for cen mRNA localization to centrosomes. This thesis aims to identify possible factors imperative for cen centrosomal localization, aspects of which may be impaired in models of centrosomal disease and dysfunction.
Table of Contents
Chapter I: Introduction..........................................................................................1
Chapter II: Results.................................................................................................9
Chapter III: Discussion..........................................................................................18
Chapter IV: Materials and Experimental Procedures.................................................23
Chapter V: References............................................................................................27
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Analysis of Factors Required for Centrocortin mRNA Localization to Centrosomes in Drosophila Embryos () | 2023-04-10 10:40:01 -0400 |
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