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Transcriptional regulation and mechanistic insights on the telomeric lncRNA TERRA

Objective

Telomeres, the heterochromatic structures that protect the ends of the chromosomes are transcribed into a novel class of long non-coding RNAs whose transcriptional regulation and functions are unknown. Telomeres protect the physical extremities of the chromosomes and they are are essential to genome integrity and stability. Dysfunctional telomeres have been detected in up to 90% of human cancers. We recently found that telomeres are transcribed from the subtelomeric region towards the end of the chromosome into the telomeric repeat-containing RNAs (TERRA). The identification of TERRA introduced a new field of research that demonstrates the structural and functional complexity unfolding at telomeres. Several lines of investigation have failed to elucidate the transcriptional activation network and functions of TERRA. The proposed research is built on a series of unrelated parts to explore the transcriptional requirements and the role of TERRA in the cells, employing a variety of different and revolutionary approaches. We plan to systematically identify the transcriptional factors that bind TERRA promoters and characterize their role in TERRA biogenesis (1). We will explore the dynamics of TERRA localization and determine if the transcripts remain attached to the sequence of origin or they can act at other chromosomal ends or loci (2). And finally we will elucidate the role of TERRA in stabilizing or recruiting telomeric or heterochromatic proteins at both telomeric and non-telomeric loci and assess their function on the chromatin (3). We expect that our innovative approaches will decipher TERRA’s localization preference on the chromatin, explore the multilayered ribonucleoprotein TERRA cluster, and it will provide new insights on plethora of telomere functions. Our studies will have a profound impact on our current understanding of the structural and functional complexity of telomeres.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

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.

(opens in new window) H2020-MSCA-IF-2015

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Coordinator

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution

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.

€ 175 419,60
Address
BATIMENT CE 3316 STATION 1
1015 LAUSANNE
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 175 419,60
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