Project description
Ribosomal frameshifts as stress regulators of cellular mRNA pool
Gene expression modulation maintains cellular homeostasis, involving the processes of transcription and RNA degradation to determine the abundance and composition of the mRNA pool. Nonsense-mediated decay (NMD) controls RNA turnover, eliminating erroneous transcripts containing premature termination codons (PTCs). Recent studies show that ribosomal frameshifts (RFs), occurring during translation, induce PTCs and initiate NMD response. Preliminary data suggest that stress regulates RFs and represents a new mechanism to sense environmental signals and adjust mRNA abundance. The EU-funded TERMINATOR project is investigating stress-dependent regulation of RFs and their role in RNA turnover, applying high-scale analysis in yeast and human cells.
Objective
Modulation of gene expression is key for maintaining cellular homeostasis in the changing environment. It is achieved through controlling the processes of transcription and RNA degradation that ultimately affect abundance and composition of the mRNA pool. Emerging evidence suggests that the pathways of RNA surveillance and degradation are of paramount importance for fast adaptation of gene expression to stress. One of the most studied mechanisms controlling RNA turnover is nonsense-mediated decay (NMD). It eliminates erroneous transcripts containing premature termination codons (PTC), and also regulates expression of functional transcripts in condition-dependent manner. Recently, my host lab has demonstrated existence of widespread coupling between mRNA decay and translation. This opens a new window for translation dependent regulation of RNA turnover. Specifically, recent studies show that ribosomal frameshifts (RF) occurring during translation induce PTCs and fire NMD response. Preliminary evidence from the host lab suggests that RF is regulated upon stress and could serve as a new mechanism to sense environmental signals and adapt mRNA concentrations. It is yet to be tested if such a regulation is of widespread nature in the cell.
The main goal of this project is to investigate stress-dependent regulation of ribosomal frameshifts and their role in RNA turnover. The 5PSeq approach developed in the host lab will allow for performing high-scale analysis in yeast and human cells, and overcoming existing technological challenges previously limiting research in the field. This project will also explore the cross-talk between RNA turnover and telomere maintenance in cellular response to stress and aging. This will expand the accumulated evidence suggesting interconnection of RNA turnover with other processes involved in cellular adaptability. Finally, I will develop a software package for analysis of RNA degradation datasets that can be used by the research community.
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 computer and information sciences software
- natural sciences biological sciences cell biology
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine physiology homeostasis
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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.1.3. - 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-EF-ST - Standard EF
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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-2018
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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.
171 77 STOCKHOLM
Sweden
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.