Genetic and genomic approaches to explore roles for the conserved 3’-5’ exoribonuclease EXOSC10 in normal and malignant cells

EXOSC10 is a conserved 3'-5' exoribonuclease involved in processing ribosomal RNAs and degrading coding and non-coding transcripts as a catalytic subunit of the nuclear RNA exosome and in cooperation with co-factors. The protein is post-translationally modified, and shuttles between the nucleolus and the nucleus in response to oxygen deprivation in a process that involves sumoylation. EXOSC10 is of medical interest because its activity is inhibited by the anti-cancer drug 5-fluorouracil, which interferes with DNA replication and RNA-dependent processes. Moreover, high expression of EXOSC10 in certain somatic tumors is associated with patient survival. We discuss global and tissue-specific deletion experiments in the mouse, assess the protein's clinical relevance as a prognostic cancer biomarker in the context of human genomics data for normal versus malignant tissues and explore EXOSC10's transcriptional regulatory network.