NRNPS & INFLAMMATION

Nuclear HuR-hnRNP interactions in post-transcriptional regulation of inflammatory gene expression

Coordinatore	BIOMEDICAL SCIENCES RESEARCH CENTER ALEXANDER FLEMING    more  Organization address address: Al. Fleming Street 34 city: VARI-ATHENS postcode: 16672 contact info Titolo: Prof. Nome: Babis Cognome: Savakis Email: send email Telefono: +30 2 109656310
Nazionalità Coordinatore	Greece [EL]
Totale costo	211˙110 €
EC contributo	211˙110 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-IEF
Funding Scheme	MC-IEF
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-12-01   -   2013-11-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	BIOMEDICAL SCIENCES RESEARCH CENTER ALEXANDER FLEMING  Organization address address: Al. Fleming Street 34 city: VARI-ATHENS postcode: 16672 contact info Titolo: Prof. Nome: Babis Cognome: Savakis Email: send email Telefono: +30 2 109656310	EL (VARI-ATHENS)	coordinator	211˙110.00

Mappa

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 Obiettivo del progetto (Objective)

'Inflammation, essential component of the innate immune response, allows multicellular organisms to repair damaged tissue. Excessive inflammation however, can itself exacerbate tissue damage, leading to chronic inflammation-related disease. The expression of crucial mediators of the inflammatory response is tightly regulated at transcriptional and post-transcriptional levels. Recent studies have shed some light on how cytoplasmic RNA processing events regulate mRNAs encoding inflammation mediators. However, it is unknown how nuclear post-transcriptional events control the expression of such molecules and what the contribution of RNA binding proteins (RBPs) in this control is. An RBP that has emerged as a pleiotropic modulator of mRNA function is HuR (Human antigen R) protein. In the cytoplasm, HuR stabilises many mRNAs via interplay with other RBPs. Research from the host laboratory has shown that over-expressed HuR represses translation of specific inflammatory mRNAs and attenuates acute inflammatory reactions, an unexpected role for HuR given its previous characterisation as an mRNA stabiliser. However, the role of HuR in the nucleus, where is most abundant, is still not understood. What is known is that nuclear HuR interacts, in an RNA dependent manner, with certain hnRNPs known to play a role in post-transcriptional regulation of gene expression. However, the role of these nuclear HuR-hnRNP interactions is unclear. The proposed research aims to understand the role of the nuclear HuR-hnRNP complexes in post-transcriptional regulation of inflammatory response in mouse macrophages. The Researcher’s expertise in studying ribonucleoprotein interactions in RNA function and processing in vitro will be combined with the Supervisor’s in functional study of post-transcriptional regulators in vivo and ex vivo. We will characterise the nuclear HuR-hnRNP complexes at both protein and RNA levels, and study their biological functions in regulating inflammatory gene expression.'

Introduzione (Teaser)

Excessive inflammation can lead to chronic diseases such as cancer and inflammatory bowel diseases. How inflammation can be regulated is key to developing possible therapies for these diseases.