Der piRNA Pathway und seine Rolle in der Regulation maternaler mRNAs während der frühen Embronalentwicklung in Drosophila.
Zusammenfassung der Projektergebnisse
The Piwi-interacting RNA (piRNA) pathway is a small RNA silencing pathway. Small RNA silencing pathways use a small RNA guide (18-30 nt) that tethers a proteins machinery to target RNA or DNA by hybridisation with the target sequence. The protein machinery of the small RNA pathway than represses gene function in numerous different ways, for example by degradation of the target mRNA. The piRNA pathway is a specialised small RNA pathway, that acts in the gonades of animals and protects here the genome against the destroying action of transposable elements (TEs). TEs are foreign genetic elements that self replicate and move in the host genome and destroy thereby the host genome. The piRNA pathway is a defence machinery against the malice action of TEs. Another function of the piRNA pathway that is now emerging, is the regulation of mRNAs that belong to the organism themself. In this project we study this newly discovered function of the piRNA pathway using the Drosophila embryo as a model. We performed iCLIP, a technique that allows to identify RNA-protein interactions, with the PIWI protein Aubergine (Aub), a component of the piRNA pathway machinery, and identify hundreds of maternal mRNAs interacting with Aub in the early Drosophila embryo. We could show that a proportion of these mRNA is degraded in Aub-dependent manner. Strikingly, these mRNAs are important for germ cell development. The same iCLIP experiments with an Aub mutant protein that is unable to bind piRNAs showed a greatly reduced binding of Aub to mRNA. This result confirms that the binding of Aub to mRNAs is mediated by piRNAs. These results suggest general regulation of maternal mRNAs by Aub and piRNAs, which plays a key developmental role in the embryo through decay and localization of mRNAs encoding germ cell determinants.
Projektbezogene Publikationen (Auswahl)
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Control of maternal mRNA stability in germ cells and early embryos. Biochimica et Biophysica Acta (2013) Jun-Jul; 1829(6-7): 714-24
Bridlin Barckmann and Martine Simonelig
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Aubergine iCLIP reveals direct regulation of mRNAs involved in germ cell development by piRNAs in the early embryo. Cell reports (2015) 12, 1-12
Bridlin Barckmann, Stéphanie Pierson, Jérémy Dufourt, Catherine Papin, Claudia Armenise, Fillip Port, Thomas Grentzinger, Séverine Chambeyron, Grégory Baronian, Jean-Pierre Desvignes, Tomaz Curk and Martine Simonelig
