The Archaeal Exosome: Degradation and Tailing at the 3′-End of RNA

Abstract

Processing of many nascent RNAs into functional molecules includes ribonucleolytic trimming at the 3′-end. Additionally, ribonucleases are needed for removal of non-functional RNAs and for mRNA degradation adjusting mRNA levels to physiological needs of the cell. In most Archaea RNA processing and degradation at the 3′-end are performed by a protein complex named exosome. The archaeal exosome degrades RNA phosphorolytically from the 3′-end releasing nucleoside 5′-diphosphates (NDPs). In a reverse reaction, it uses NDPs to synthesize heteropolymeric, adenine-rich tails at the 3′-end of RNAs dedicated to degradation. The exosome consists of a hexameric ring structure composed of the archaeal proteins aRrp41 and aRrp42, and of a multimeric RNA-binding cap containing three different proteins (aRrp4, aCsl4 and aDnaG) with totally four different RNA binding domains (S1, KH, Zn-ribbon and the N-terminal domain of aDnaG). The hexameric ring and a variable aRrp4-aCsl4-heterotrimer form the nine-subunit core of the archaeal exosome, a structure that is evolutionary preserved in the bacterial polynucleotide phosphorylase (PNPase) and in the eukaryotic exosome. However, while in most eukaryotic exosomes the nine-subunit core is catalytically inactive, both bacterial PNPase and the archaeal exosome contain three phosphorolytic sites in the channels of their hexameric rings and function as exoribonucleases and RNA tailing enzymes. aDnaG is the archaea-specific subunit of the archaeal exosome and probably increases its substrate versatility, contributes to the regulation of its functions and determines its subcellular localization.