EJC_SPLIC_HET

Role of the exon junction complex in the splicing of heterochromatic transcripts

Coordinatore	INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH    more  Organization address address: ACKERMANNWEG 4 city: MAINZ postcode: 55128 contact info Titolo: Ms. Nome: Franziska Cognome: Martin Email: send email Telefono: +49 6131 39 21453 Fax: +49 6131 39 21421
Nazionalità Coordinatore	Germany [DE]
Totale costo	100˙000 €
EC contributo	100˙000 €
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-2012-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-03-01   -   2017-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH  Organization address address: ACKERMANNWEG 4 city: MAINZ postcode: 55128 contact info Titolo: Ms. Nome: Franziska Cognome: Martin Email: send email Telefono: +49 6131 39 21453 Fax: +49 6131 39 21421	DE (MAINZ)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Pre-mRNA splicing is an essential function in virtually all eukaryotic organisms. In the human genome, 95% of the genes with multiple exons are subjected to alternative splicing, increasing the diversity of the transcriptome and ensuring the complexity of the organism. Because of its prevalence in many physiological functions splicing mis-regulation has been linked to a large number of diseases, including various cancers. In addition to providing diversity splicing presents an opportunity for genetic control at multiple layers of its regulation. One of these layers is the cis-regulatory elements present on the transcripts, and their associations with their cognate trans-acting factors. The coupling between transcription and splicing introduces additional regulatory levels. For instance, an unexpected connection between chromatin and splicing has recently been uncovered. However, despite its potential significance, we still know very little about how these two processes communicate with each other. We have recently found an essential role for the exon junction complex (EJC) in the splicing of long introns in Drosophila. Remarkably, this function is biased towards transcripts encoded by genes located in heterochromatin, suggesting that heterochromatic transcripts containing long introns might be spliced by a novel mechanism in which the EJC plays a crucial role. We plan to decipher the mechanism by which the EJC regulates splicing of large heterochromatic transcripts and more generally how heterochromatin influences pre-mRNA splicing. This study will have a major impact on our understanding of the interplay between chromatin and splicing and should lead to alternative therapeutic strategies which will involve the modulation of chromatin to treat human diseases that are a consequence of aberrant splicing. Furthermore, this project should contribute to the understanding of the long-standing paradox of how gene expression can occur from a heterochromatic environment.'