Objective
To date, mechanistic studies on the macromolecular complexes that synthesize or degrade RNAs or proteins have investigated these machines individually to understand how they execute different steps in the gene expression process. Although the individual complexes catalyze their reactions independently of each other in vitro, increasing evidence suggests that they function in a highly coordinated manner in vivo. The molecular basis for such a coordination remains largely unknown. During the past five years, our group has focused on deciphering the mechanisms of multiprotein complexes that mediate mRNA turnover in S. cerevisiae. Here, I propose to take these analyses to the next level and visualize how a major RNA degradation machine, the exosome, is directly coupled to the protein-synthesis machine, the ribosome. In particular, we want to study two different exosome-ribosome assemblies that underpin opposite outcomes of RNA degradation: a constructive function of the nuclear exosome in the maturation of the large ribosomal subunit and a destructive function of the cytoplasmic exosome in the elimination of ribosome-bound mRNAs. Building on our preliminary data from both the yeast and human systems, we will use a combination of bottom-up biochemical reconstitutions and top-down endogenous purifications to isolate 1) an exosome complex and its nuclear cofactors bound to a pre-60S ribosomal subunit and 2) an exosome complex and its cytoplasmic cofactors bound to a stalled 80S ribosome. We will determine the structures of these ~3 - 4 MDa nuclear and cytoplasmic assemblies using the combined information from cryo-electron microscopy and X-ray crystallography approaches. The structural studies, combined with biochemical and genetic information, will reveal how these machines interact and coordinate RNA metabolism with protein synthesis. Overall, this work will provide important insight into the principles that coordinate different steps of eukaryotic gene expression.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences genetics RNA
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-ADG - Advanced Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2016-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
80539 MUNCHEN
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.