mRNA localization and local translation is a common mechanism for efficient protein expression and function control and plays a crucial role in processes such as cell fate determination and polarity and axonal guidance. One of the better-studied systems for RNA localization is the Drosophila oocyte, in which the microtubule-dependent asymmetric localization of specific transcripts determines the fly body axes. RNA degradation and translational control factors are implicated in mRNA localization, as exemplified by the mislocalization of osk mRNA, the posterior determinant, in mutants of RNAi-associated proteins (e.g. Aub, Armi, Spn-E) and P-body components (Me31B, Dcp-1). The aim of this project is to investigate the role of the RNA degradation and translational control machinery in mRNA localization. The osk mislocalization phenotype in the RNAi-related mutants is related to the derepression of retrotransposons and consequent activation of the DNA damage checkpoint and of Mnk/Chk2. Our data suggest, however, that the phenotype is ultimately due to an impaired actin mesh and consequent premature ooplasmic streaming. I will therefore study the molecular link between DNA damage checkpoint activation and premature ooplasmic streaming, using Drosophila genetics and biochemical and molecular biology tools. Candidate players in the process are, obviously, actin regulators, but also the translation regulators Orb/CPEB and Bic-C, since premature ooplasmic streaming also occurs in hypomorphic orb mutants and in Bic-C overexpression. P-body components colocalize with osk mRNA at the posterior and are genetically required for proper osk mRNA localization, suggesting that they play a role in osk mRNP formation and/or transport. In order to study the relationship between P-bodies and osk mRNA localization, I will peform dual-labeled time-lapse imaging of osk mRNA and P-body components.
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