Objective "The degradation of mature mRNAs has emerged as a key step in the regulation of eukaryotic gene expression. Modulation of the half-life of mRNAs via their degradation is a powerful and versatile mechanism to swiftly alter the expression of proteins in response to changes in physiological conditions. The decay of mRNAs is performed by a set of macromolecular complexes that act in a sequential and coordinated manner, progressively eroding the ends of the transcript until its degradation is complete. These macromolecular assemblies contain only a few catalytically active subunits and a large number of regulatory components. How and why the activities are regulated within the architecture of the complexes is largely unknown. Also unclear are the mechanisms with which the complexes communicate with each other and/or with the changing composition of the nucleic acid. In this project, we will reconstitute the key protein complexes in mRNA decay from recombinant proteins in vitro. Specifically, we will focus on the evolutionary conserved deadenylation, decapping and exosome-Ski complexes. The reconstituted complexes will be used for structural studies to derive atomic models of the holoenzymes using a combination of X-ray crystallography and cryoelectron microscopy. In parallel to obtaining static views of the individual steps in the pathway, we will establish the assays to study how information from one processing step is passed on to the next in a dynamic manner. We will address the basis for the timing and interrelationship of the conserved enzymatic machineries and the influence of the mRNP composition on their activity. Our final goal is to recapitulate the complex behavior of the mRNA decay pathway in vitro. Our lab has extensive experience in biochemical reconstitution of protein complexes, in vitro biochemical assays and X-ray crystallography. In the next five years, we plan to implement cryoelectron microscopy within the scope of this proposal." Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesearth and related environmental sciencesgeologymineralogycrystallographynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopynatural sciencesbiological sciencesgeneticsRNA Programme(s) 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) Topic(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2011-ADG_20110310 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV EU contribution € 2 499 344,00 Address HOFGARTENSTRASSE 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Anne Katrin Werenskiold (Dr.) Principal investigator Elena Conti (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germany EU contribution € 2 499 344,00 Address HOFGARTENSTRASSE 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Anne Katrin Werenskiold (Dr.) Principal investigator Elena Conti (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
