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

Abstract

EXOSC10 is a conserved 3′-5′ exoribonuclease involved in processing ribosomal RNAs and degrading coding and noncoding transcripts as a catalytic subunit of the nuclear RNA exosome and in cooperation with cofactors. The protein is posttranslationally 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 anticancer 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.