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Specificity of translational control during unfolded protein response

Obiettivo

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.

Invito a presentare proposte

ERC-2013-CoG
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Meccanismo di finanziamento

ERC-CG - ERC Consolidator Grants

Istituzione ospitante

UNIVERSITY COLLEGE LONDON
Contributo UE
€ 1 999 435,00
Indirizzo
GOWER STREET
WC1E 6BT LONDON

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Tipo di attività
Higher or Secondary Education Establishments
Contatto amministrativo
Giles Machell (Mr.)
Ricercatore principale
Jernej Ule (Prof.)
Collegamenti
Costo totale
Nessun dato

Beneficiari (1)