Towards a mechanistic understanding of mRNA locali.. (RNPlocalization)
Towards a mechanistic understanding of mRNA localization
Start date: Jan 1, 2013,
End date: Dec 31, 2017
The localization of mRNAs has been increasingly recognized as a prominent mode of regulation of gene expression in eukaryotes. Localized RNAs can have crucial roles during animal development, in the maintenance of cell polarity and in nervous system function. Studies of RNA localization in model organisms have revealed many components of the process, some of which are conserved across eukaryotes. The correct cytoplasmic localization of mRNAs and their transport and silencing in messenger ribonucleoprotein particles (mRNPs), is dependent on the earliest steps of mRNA processing in the nucleus. The core nuclear mRNP particles associate with further components in the cytoplasm, forming large and dynamic multimolecular assemblies, underlying the various steps or mRNA maturation, transport, silencing and eventual localized translation. Even though many components of these large mRNP particles are known, their detailed molecular organization and regulation is poorly understood. Our aim is to gather structural information of mRNP complexes involved in RNA localization in the fruit fly Drosophila, currently the best-studied model system. We will use a multidisciplinary approach, combining biochemistry, protein crystallography and fly genetics, to tackle the complex structure-function relationships regulating mRNA localization. Our work will elucidate the structural details and molecular mechanisms of how mRNP complexes regulate mRNA localization during development. Given that mRNA localization is a conserved process, our results are expected to elucidate the mechanistic and structural details of a conserved regulatory pathway with fundamental and often medically relevant roles in the cell.
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