MRNA QUALITY

Quality control of gene expression: mechanisms for recognition and elimination of nonsense mRNA

Coordinatore	UNIVERSITAET BERN    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Switzerland [CH]
Totale costo	1˙300˙000 €
EC contributo	1˙300˙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-2007-StG
Funding Scheme	ERC-SG
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-06-01   -   2013-05-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITAET BERN  Organization address address: Hochschulstrasse 4 city: BERN postcode: 3012 contact info Titolo: Dr. Nome: Oliver Cognome: Mühlemann Email: send email Telefono: -6314617 Fax: -6314606	CH (BERN)	hostInstitution	0.00
2	UNIVERSITAET BERN  Organization address address: Hochschulstrasse 4 city: BERN postcode: 3012 contact info Titolo: Ms. Nome: Maddalena Cognome: Tognola Email: send email Telefono: 0041 31 631 4809 Fax: 0041 31 631 5106	CH (BERN)	hostInstitution	0.00

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 Obiettivo del progetto (Objective)

'Analogous to quality control checks along the assembly line in industrial manufacturing processes, cells possess multiple quality control systems that ensure accurate expression of the genetic information throughout the intricate chain of biochemical reactions. “Nonsense-mediated mRNA decay” (NMD) represents a quality control mechanism that recognizes and degrades mRNAs of which the protein coding sequence is truncated by the presence of a premature termination codon (PTC). By eliminating these defective mRNAs with crippled protein-coding capacity, NMD substantially reduces the synthesis of potentially deleterious truncated proteins. Given that 30 % of all known disease-causing mutations in humans lead to the production of a nonsense mRNA, NMD serves as an important modulator of the clinical manifestations of genetic diseases, and manipulating NMD therefore represents a promising strategy for future therapies of many genetic disorders. However, the underlying molecular mechanisms of NMD are currently not well understood. One goal of our research is to understand at the molecular level how PTCs are recognized and distinguished from correct termination codons and how this recognition of nonsense mRNAs subsequently triggers their rapid degradation. In addition to triggering NMD, we have recently discovered that PTCs in certain immunoglobulin genes can also lead to the transcriptional silencing of the corresponding gene. We now search for the biological relevance of this novel quality control mechanism termed “nonsense-mediated transcriptional gene silencing” (NMTGS) and want to identify the involved molecules and their interactions. Using mainly mammalian cell cultures, we study the effect on the expression of engineered NMD and NMTGS reporter genes upon various treatments of the cells. State-of-the-art biochemical and molecular biology techniques are employed with the goal to further our understanding of these processes and their regulation at the molecular level.'