Ricerc@Sapienza

Cellular senescence describes an irreversible growth arrest characterized by distinct morphology, gene expression pattern, and secretory phenotype. Cellular senescence can be induced by several stimuli including DNA damage, telomere dysfunction, oxidative stress, oncogene activation and organelle stress. The accumulation of senescent cells has been linked to embryogenesis, cancer, organismal ageing and age-related disorders. Moreover, cellular senescence is associated with extensive reprogramming of the epigenetic landscape, including histone modifications and formation of senescence-associated heterochromatic foci (SAHF).

The miRNA machinery components act as post-transcriptional regulators of messenger RNA targets via mRNA degradation and/or translational repression. However in the last few years there have been several reports indicating that miRISC machinery are also present in mammalian cell nuclei where they are implicated in the creation and/or maintenance of heterochromatin at various sites throughout the genome. In particular, recent studies highlight a role of Ago2, the main miRNAs effector protein, into the nuclei of senescent cells in which in could be required to guide SAHF assembly and chromatin reorganization.

Our project aim to elucidate the nuclear role of Ago2 in cellular senescence, focusing on the identification of the Ago2 molecular partners required to modulate the senescent phenotype. In parallel, we are interested to understand the molecular mechanism regulating Ago2 redistribution between cytoplasm and nucleus during senescence. To this aim, the project employs cellular, pharmacological and biochemical protocols, using both primary fibroblasts and doxorubicin treated cancer cells, on which our lab has a consolidated expertise