Telomeres are heterochromatic nucleoprotein structures located at the end of linear eukaryotic chromosomes. Telomeres allow cells to distinguish between natural chromosome termini and double-stranded breaks in the DNA and also set the lifespan of normal somatic cells by eliciting cellular senescence when they become critically short. Loss of proper telomere structure triggers severe chromosomal instability cascades, which are hallmarks of many human diseases including cancer. The heterochromatic nature of telomeres and their gene-less nature suggested the idea that telomeres are transcriptionally silent genomic regions. On the contrary, we have recently discovered that mammalian telomeres are transcribed into TElomeric Repeat containing RNA (TERRA). TERRA molecules are transcribed from several subtelomeric loci towards chromosome ends and localize to telomeres. We have also shown that some ‘Suppressors with Morphogenetic Defects in Genitalia’ (SMG) proteins, which are effectors of an RNA surveillance pathway known as ‘Nonsense-Mediated mRNA Decay’ (NMD), are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin and safeguard telomere integrity.

Our laboratory exploits a variety of molecular genetic, biochemical and cell biological approaches in order to characterize TERRA structure and function, using cultured human and mouse cells as model systems.

We are currently addressing crucial questions about TERRA biogenesis and putative TERRA-associated functions in maintaining telomere architecture in normal, cancer and senescent cells. We are also trying to dissect the molecular events leading to accumulation of telomere-associated TERRA and to telomere dysfunctions in cells compromised for SMG functions.

With these goals, we hope to contribute to expand the current understanding of how normal telomere structure is maintained and to disclose novel cellular pathways involved in cancer and senescence etiology.