ARN decay
Molecular contribution of the DIS3 and SKIV2L mRNA decay factors to development and pathologies in a mammalian model organism
USIAS Fellow : Bertrand Séraphin
Post-doc: Mélanie Mahé
mRNA decay is a key cellular process that swiftly regulates protein production in response to condition changes and eliminates faulty transcripts. Complexes and protein factors making the eukaryotic mRNA degradation machinery have been identified and are largely conserved. They act in a sequential and coordinated manner to attack transcript extremities before destroying the mRNA body. Their molecular functions were so far mostly analyzed in simple eukaryotes and mammalian cultured cells. Several key questions remain to be addressed to fully understand RNA decay in mammalian organisms. This includes in particular its physiological roles, contribution to development and pathological implications. This issue will be addressed by building and analyzing transgenic mice carrying mutations in the exosome catalytic subunit DIS3 and in SKIV2L, a subunit of the cytoplasmic exosome activating complex. This project will provide new knowledge of mRNA decay and of its impact on development and disease in a mammalian model system.