Objective
RNA has gained significant attention in the past few decades due to its evolutionary role in gene regulations. In the regulation process RNA seldom works as an individual entity rather associated with several protein-protein complexes (PPCs) and those complexes play a key role in mRNA maturation. Typically, mRNA undergoes different post-transcriptional modifications and deadenylation is one of those post-transcriptional events in which shortening of the poly(A) tail at the 3 end of mRNA occurs and it plays a major role in mRNA stability. Deadenylation is often regulated by different PPCs and dysregulation of these complexes severely impaired this process. In fact, in many cancer cells shortening of poly(A) tail has been found due to the non-specific deadenylation event. Therefore, Chemical modulators that can regulate the deadenylation process have immense therapeutic importance. CCR4-NOT is one of the most studied deadenylase complexes which actively participate in the deadenylation process. Several types of mRNA-associated proteins (NOT4, Bam, and Roquin) are known which recruit RNA to the CCR4-NOT complex for deadenylation by interacting with CAF40 through its evolutionary conserved site CAF40 binding motif (CBM) domain. Moreover mRNA-associated proteins and RNA both share the same binding surface of the CAF40 protein. Therefore, blocking the interaction between CAF40 and RNA would serve the inhibitory activity of the CCR4-NOT complex towards the deadenylation process. From crystal structure, it has been found that the CBM domain of Bam protein interacts with the CAF40 protein through its -helical surface. Here in this proposal, we will design -helical hydrocarbon stapled peptide analogues of CBM domain to exploit the protein-RNA interaction by regulating the activity of CCR4-NOT complex towards deadenylation process. Several biophysical, computational, and cell-based assays will be utilized to investigate the activity and mechanism of deadenylation process.
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 chemical sciences organic chemistry hydrocarbons
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2021-PF-01
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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.