Project description
Understanding the regulatory information contained in 5′UTRs
In eukaryotes, translation starts at the mRNA 5' end, consisting of the 5' cap and 5' untranslated region (5'UTR), with protein synthesis being primarily regulated at the translation initiation step by elements within the 5'UTR. However, the role of 5'UTRs in the regulation of the dynamics of mRNA translation during vertebrate embryogenesis remains obscured. More importantly, metazoan embryos are transcriptionally silent after fertilisation, and embryogenesis is controlled by maternal factors. Developmental progression requires the synthesis of new mRNAs and proteins to be highly coordinated. The goal of the EU-funded devUTRs is to uncover the in vivo 5'UTR role in mRNA translational regulation during zebrafish embryogenesis.
Objective
Following fertilisation, metazoan embryos are transcriptionally silent, and embryogenesis is controlled by maternally deposited factors. Developmental progression requires the synthesis of new mRNAs and proteins in a coordinated fashion. Many posttranscriptional mechanisms regulate the fate of maternal mRNAs, but it is less understood how translational control shapes early embryogenesis. In eukaryotes, translation starts at the mRNA 5′ end, consisting of the 5′ cap and 5′ untranslated region (UTR). Protein synthesis is primarily regulated at the translation initiation step by elements within the 5′UTR. However, the role of 5′UTRs in regulating the dynamics of mRNA translation during vertebrate embryogenesis remains unexplored. For example, all vertebrate ribosomal protein (RP) mRNAs harbor a conserved terminal oligopyrimidine tract (TOP) in their 5′UTR. RP levels must be tightly controlled to ensure proper organismal development, but if and how the TOP motif mediates RP mRNA translational regulation during embryogenesis is unclear. Overall, we lack a systematic understanding of the regulatory information contained in 5′UTRs. In this work, I aim to uncover the 5′UTR in vivo rules for mRNA translational regulation during zebrafish embryogenesis. I propose to apply imaging and biochemical approaches to characterise the role of the TOP motif in RP mRNA translational regulation during embryogenesis and identify the trans-acting factor(s) that bind(s) to it (Aim 1). To systematically assess the contribution of 5′UTRs to mRNA translational regulation during zebrafish embryogenesis, I will couple a massively parallel reporter assay of 5′UTRs to polysome profiling (Aim 2). By integrating the translational behaviour of 5′UTR reporters throughout embryogenesis with sequence-based regression models, I anticipate to uncover novel cis-regulatory elements in 5′UTRs with developmental roles.
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 biological sciences developmental biology
- medical and health sciences clinical medicine embryology
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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-2019
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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.
4051 Basel
Switzerland
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