PAPS&PUPS

Regulation of Gene Expression by non-canonical poly(A) and poly(U) polymerases

Coordinatore	INSTYTUT BIOCHEMII I BIOFIZYKI POLSKIEJ AKADEMII NAUK    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Poland [PL]
Totale costo	1˙500˙000 €
EC contributo	1˙500˙000 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2012-StG_20111109
Funding Scheme	ERC-SG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-02-01   -   2018-01-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTYTUT BIOCHEMII I BIOFIZYKI POLSKIEJ AKADEMII NAUK  Organization address address: PAWINSKIEGO 5A city: WARSZAWA postcode: 02 106 contact info Titolo: Prof. Nome: Andrzej Cognome: Dziembowski Email: send email Telefono: 48225922033 Fax: 48225922190	PL (WARSZAWA)	hostInstitution	1˙500˙000.00
2	INSTYTUT BIOCHEMII I BIOFIZYKI POLSKIEJ AKADEMII NAUK  Organization address address: PAWINSKIEGO 5A city: WARSZAWA postcode: 02 106 contact info Titolo: Prof. Nome: Piotr Cognome: Zielenkiewicz Email: send email Telefono: 48225922145 Fax: 48225922190	PL (WARSZAWA)	hostInstitution	1˙500˙000.00

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 Obiettivo del progetto (Objective)

'In eukaryotes, almost all RNA molecules are processed at their 3’ ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases (PAPs). Recently, several new non-canonical poly(A) (ncPAPs) and poly(U) polymerases (PUPs) have been discovered that have more specific regulatory roles. In contrast to canonical ones, their functions are more diverse; some induce RNA decay while others, especially cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. Knowledge about ncPAPs and PUPs is very scarce and there are crucial questions about their functions that need to be addressed. The project has 3 parts: 1) Functional analysis of FAM46 proteins, which, according to our preliminary data, constitute a new family of active poly(A) polymerases. FAM46C is frequently mutated in myelomas and mutations in its mouse orthologue cause anaemia, thus demonstrating important biological functions of this unexplored family of proteins. 2) Elucidation of the functions of all known vertebrate ncPAPs and PUPs (7 previously known and 4 members of FAM46 family) using the chicken DT40 cell line as a model system. DT40 has an exceptionally high rate of homologous recombination, allowing easy gene targeting and generation of multiple knockouts that facilitate the study of proteins with overlapping functions. 3) Cytoplasmic polyadenylation of dormant mRNA molecules activates translation in neurons, gametes and reticulocytes. In neurons, it occurs in axons and dendrites following synaptic stimulation while in oocytes, it is induced by progesterone. The exact impact on gene expression is not well defined due to a lack of technologies identifying cytoplasmically polyadenylated transcripts. We will develop a novel detection method for ongoing RNA polyadenylation to assess the biological significance of cytoplasmic polyadenylation. This part of the project will be developed using mouse synaptoneurosomes and then transferred to reticulocytes and possibly oocytes.'