RNA Decay by the Eukaryotic Exosome

Abstract

The eukaryotic RNA exosome is a multi-subunit protein complex that regulates RNA processing and decay in processes that maintain the quality and abundance of cellular RNA. The subunit composition and activities of eukaryotic exosomes were determined by reconstituting exosomes from yeast and human. The structure of the ∼300 kDa nine-subunit human exosome revealed the architecture for the asymmetric nine-subunit eukaryotic exosome core. While the eukaryotic exosome core resembles that of bacterial PNPase and archaeal exosomes, eukaryotic exosomes differ fundamentally from their bacterial and archaeal counterparts because they do not catalyze phosphorolytic exoribonuclease activity. In contrast, hydrolytic activities within the yeast ten- (Rrp44) or eleven-subunit (Rrp44 + Rrp6) exosomes can be fully attributed to the processive or distributive activities of Rrp44 and Rrp6, respectively. While the activities of yeast Rrp44 and Rrp6 explain most activities of the eukaryotic exosome in yeast, the activities of human Rrp44 or Rrp6 have not been analyzed in any detail. In fact, human Rrp44 has not been isolated as a stable constituent of human exosomes. Current efforts are focused on characterizing activities for human counterparts to yeast Rrp44 and Rrp6 and on defining substrate preferences for the yeast exosome complexes and associated subunits through kinetic analysis using defined substrates to determine how the nine-subunit core contributes to RNA processing and decay.