Project description
Active mRNA regulation during translation
In eukaryotic cells, gene expression regulation takes place at the genomic level, as well as during or after transcription and translation. mRNA processing, export and stability constitute important parameters in this complex process. Scientists of the EU-funded mRNA-DEG-RIBOSOME project are investigating the active regulation of mRNA while it is being translated by the ribosome. In particular, they are studying the role of the emerging polypeptides and how they attract specific recognition factors that may degrade mRNA as it is being translated. The work will provide mechanistic insight into the tubulin mRNA feedback loop, which is critical for mitosis and faithful chromosome segregation.
Objective
Cell tightly regulate mRNA processing, localisation and stability to ensure accurate gene expression in diverse cellular states and conditions. Most of these mRNA regulation steps have traditionally been thought to primarily happen before translation. However, recent discoveries highlight the role of nascent polypeptides on translating ribosomes in the active regulation of mRNAs. As the nascent protein emerges from the ribosome, it marks the identity of the encoding mRNA by its unique amino acid sequence. This allows cotranslational engagement by specific polypeptide recognition factors on the ribosome, providing them access to the associated mRNA. A striking example for such regulation is the negative feedback loop in the expression of tubulins known as “tubulin autoregulation”. In this case, tubulin mRNA is degraded cotranslationally when cells sense excess free tubulin, which is critical during mitosis to ensure faithful chromosome segregation. Recently, the first specific factor in this pathway has been identified: TTC5 recognises the N-terminus of nascent tubulin emerging from the translating ribosome and triggers degradation of the associated mRNA. However, the events leading to tubulin mRNA decay downstream of TTC5 remain elusive.
In mRNA-DEG-RIBOSOME I will use tubulin autoregulation as a model system to study how the nascent chain on translating ribosomes directs mRNA degradation. Specifically, I aim to: (1) identify factors acting downstream of TTC5 required for tubulin mRNA degradation using cutting-edge mass spectrometry and genetic screening methods; (2) understand the mechanistic role of each factor in TTC5-directed mRNA degradation by using a powerful in vitro reconstitution approach; and (3) expand the understanding of nascent chain-dependent mRNA degradation by investigating related feedback systems. Thus, my work will to provide a conceptual framework for how cells have evolved to exploit nascent polypeptide recognition to direct mRNA fate.
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 biological sciences biochemistry biomolecules proteins
- natural sciences chemical sciences organic chemistry amines
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences genetics chromosomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2020
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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.
SN2 1FL SWINDON
United Kingdom
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.