Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
ReviewRNA decay machines: The exosome☆
Highlights
► The eukaryotic exosome is a major ribonuclease for RNA decay and processing. ► The repertoire of catalytic subunits varies among Eukaryota. ► Some catalytic subunits are compartment-specific and give rise to exosome isoforms. ► Substrate threading modulates ribonuclease activities in the holocomplex. ► The many cellular functions of the exosome are mediated by auxiliary factors.
Section snippets
Part One: exosome structure
The eukaryotic exosome is composed of ten to eleven subunits, which can be divided into two major groups with regard to their structural and functional contributions. The first group encompasses nine proteins that form the ‘exosome core’. They are all rather small polypeptides with molecular masses of 20–50 kDa. Three of these are built entirely of RNA binding domains and motifs, whereas the remaining six are single-domain proteins homologous to RNase PH, a homomultimeric enzyme found in
Part two: catalytic properties and mechanisms of the exosome
Despite their structural similarity, the catalytic properties of the eukaryotic exosome core and the prokaryotic exosome core-like complexes are very different. While the latter are endowed with phosphorolytic ribonuclease activity residing in the RNase PH-like domains, the former is completely inactive. Instead, the exosome of Eukaryota has three hydrolytic ribonuclease activities, which are supplied by the associated subunits of the Dis3 and Rrp6 families. However, even though it has no
Part three: the exosome in vivo
Considering its complicated structure and array of catalytic activities, the exosome is far more than just another nuclease. It targets RNAs of virtually all classes at various stages of their lives, from maturation through constant quality control to final turnover. Its functions are, among others, maturation of 3′ ends of rRNA and snoRNAs, degradation of unstable RNAs generated by pervasive and read-through transcription, removal of excised introns and other RNA maturation by-products,
Conclusion
With its multi-subunit structure and three different ribonuclease activities, tightly regulated and applied to vastly different purposes (house-keeping and regulatory), the exosome is a truly amazing machine. While its importance was never questioned, it is only in recent years that its functional diversity has been fully appreciated, and still new surprising roles of the exosome are being uncovered [102], [103]. The various auxiliary systems that govern exosome substrate recruitment form an
Note added in proof
When this article was in press, a study by Makino et al. (http://dx.doi.org/10.1038/nature11870) revealed new information about the structure of the holoexosome of S. cerevisiae, specifically the binding site of Rrp6 and details of substrate threading through the core complex. We strongly suggest that the article be read along with this review.
Acknowledgements
ADZ's group is supported by National Science Center grants: 3339/B/P01/2010/39 and 2011/02/A/NZ1/00001. THJ's group is supported by the Danish National Research Foundation, the Novo Nordisk Foundation and the Danish Cancer Society. ML was supported by a PhD fellowship of the Boehringer Inhelgeim Fonds. The authors wish to thank Karolina Drążkowska for critical reading of the manuscript.
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This article is part of a Special Issue entitled: RNA Decay mechanisms.