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 medical and health sciencesmedical biotechnologygenetic engineeringmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticschromosomes Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE Net EU contribution € 175 419,60 Address BATIMENT CE 3316 STATION 1 1015 Lausanne Switzerland See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 175 419,60
