An investigation of nutrition-dependent mRNA translation in Drosophila larvae

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Dietary nutrients promote organismal growth via activation of cellular pathways that are necessary for cellular growth and division. However, upon conditions of nutrient scarcity, organisms ranging from yeast to mammals alter their metabolism to conserve nutrients and energy. One of the key cellular events required for sustained growth downstream of nutrition is mRNA translation. In order to coordinate cellular and organismal growth with nutrient availability, organisms have devised several control checkpoints to limit the energy consuming process of translation under starvation. Work on mammalian cell lines have shown that mRNA translation is inhibited in response to a multitude of stresses including nutritional stress, DNA damage, viral stress, hypoxia and oxidative stress. However, it is unclear as to how an organism in general responds to starvation in terms of mRNA translation. I have used polysome gradient analysis in developing Drosophila larvae to show that starvation led to a rapid decrease in translation, seen as early as 30 minutes after removal of larvae from food. A maximal decrease in translation was observed after 6-18 hours of starvation. Using qRT-PCR I have looked at the translation profile of 18 individual genes and observed that starvation led to a general decrease in translation, irrespective of the starvation-mediated change in total transcript levels. Sugars and amino acids have been shown to be important regulators of translation in animal cells. I have determined that neither sugars nor amino acids were sufficient to maintain translation in larvae removed from food. However, a complex diet such as yeast was sufficient to maintain translation in larvae removed from food. The majority of work in the field of translation suggest three main signaling pathways functioning downstream of nutrition to regulate translation - insulin signaling,TOR signaling and eIF2α signaling. I have shown that TOR signaling is required for translation in fed conditions. On the other hand, genetic activation of TOR and/or insulin signaling was not sufficient to prevent the starvation-mediated inhibition of translation. I have also shown that the eiF2α kinases - GCN2 and PERK were not required for starvation-mediated suppression of translation.
Genetics, Biology--Molecular
Nagarajan, S. (2015). An investigation of nutrition-dependent mRNA translation in Drosophila larvae (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from doi:10.11575/PRISM/24913