Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

FP7

ASCE Sintesi della relazione

Project ID: 630758
Finanziato nell'ambito di: FP7-PEOPLE
Paese: Czech Republic

Periodic Report Summary 1 - ASCE (Aberrant Splicing of CFTR Exon 9)

In this project, Peter Josef Lukavsky (PJL) uses a multidisciplinary approach to study the regulatory RNA-protein and protein-protein interactions surrounding the aberrantly spliced cystic fibrosis transmembrane conductance regulator (CFTR) exon 9. This unfavourable splicing event depends primarily on DNA variations in the polymorphic (TG)mTn locus upstream of exon 9. On the pre-mRNA level, this locus generates an extended UG-rich binding site for TDP-43 (43 kDa TAR DNA binding protein) which - in concert with recruitment of hnRNP A1/A2 (heterogeneous nuclear ribonucleoprotein A1/A2) - prevents recognition of the 3’ splice site (ss) of exon 9 by the splicing machinery. Thus exon 9 is excluded from the spliced mRNA and this results in a non-functional protein product associated with severe forms of cystic fibrosis (CF). PJL’s research tools range from binding measurements and structural techniques to functional assays and HTS screening for small molecule inhibitors.

Contatto

Vladimir Sklenar, (Programme Coordinator)
Tel.: +420549497022
E-mail

Argomenti

Life Sciences
Numero di registrazione: 183902 / Ultimo aggiornamento: 2016-06-10
Fonte d'informazione: SESAM