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Specificity of translational control during unfolded protein response (TRANSLATE)
Start date: Mar 1, 2014, End date: Feb 28, 2019 PROJECT  FINISHED 

Unfolded protein response (UPR) is activated by multiple types of cellular stress, and can promote either cell survival or apoptosis. The balance between these opposing outcomes is delicately regulated, and when lost, contributes to diverse diseases. UPR enables cells to halt general translation, while inducing translation and transcription of specific mRNAs that escape repression. Even though the general machinery controlling translation is well understood, several fundamental open questions remain: 1) how are mRNAs selected for translation during UPR, 2) what role does mRNA structure and sequence play in this selection, 3) what role does UPR pathway play in the highly differentiated cells, such as neurons? My lab employs an integrative approach to understand how RNA-binding proteins (RBPs) control specific mRNAs. We recently developed hiCLIP, a method that globally quantifies interactions between RBPs and double-stranded RNA in live cells. Our preliminary findings demonstrate that a double-stranded RBP binds to structured motifs in mRNAs to control stress-induced translation. I propose to determine how combinatorial recognition of RNA sequence and structure by RBPs controls mRNA localisation, stability and translation during UPR. In addition, we will assess the role of UPR pathway in neuronal differentiation. Taken together, this study aims to elucidate how cells select specific mRNAs for translation, and thereby survive during stress or respond to signals that control differentiation.

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