Objective
More than 70% of the human genome synthesizes non-coding RNA that is believed to regulate gene expression. While there is ample evidence from model systems that small RNAs are the lynchpin of powerful mechanisms that silence transcription, the demonstration of transcriptional gene silencing (TGS) mediated by a small RNA in humans is lacking. We have recently shown that the HIV-1 LTR is controlled by premature termination of transcription and TGS mediated by a small RNA derived from the stem-loop structure, TAR, that forms the 5’ end of HIV-1 transcripts. This pathway depends on Microprocessor, Xrn2, Setx and Rrp6. Cleavage of TAR by Microprocessor has major consequences 1) it provides a substrate for Rrp6, which generates a small RNA that represses HIV-1 transcription, 2) it creates an entry site for Xrn2 and termination factors that lead to premature termination of transcription. Loss of Microprocessor or Rrp6 leads to recruitment of RNAPII to the LTR and activation of transcription. These findings not only provide the first evidence showing that small RNA-mediated TGS acts in human cells, but they also uncovered a new mechanism of gene regulation involving premature termination of transcription by RNAPII. Several important questions now need to be answered. What is the mechanism underlying small RNA-mediated TGS? Does small RNA-mediated TGS operate at human genes? What is the contribution of TGS coupled to premature termination in the global control of transcription? We will use a battery of biochemical and molecular approaches to dissect the molecular mechanism of RNA-mediated TGS. The global importance of small RNA-mediated TGS and premature termination of transcription in the control of human gene expression will be addressed using complementary genome-wide approaches. RNA-mediated TGS coupled to premature termination, if confirmed as a widespread mechanism controlling transcription, will fundamentally change our perspective of transcriptional control in humans
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering computer hardware computer processors
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
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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.
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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2013-CoG
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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.
Host institution
75794 Paris
France
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.