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The archaeal exosome core is a hexameric ring structure with three catalytic subunits

Abstract

The exosome is a 3′ → 5′ exoribonuclease complex involved in RNA processing. We report the crystal structure of the RNase PH core complex of the Sulfolobus solfataricus exosome determined at a resolution of 2.8 Å. The structure reveals a hexameric ring-like arrangement of three Rrp41–Rrp42 heterodimers, where both subunits adopt the RNase PH fold common to phosphorolytic exoribonucleases. Structure-guided mutagenesis reveals that the activity of the complex resides within the active sites of the Rrp41 subunits, all three of which face the same side of the hexameric structure. The Rrp42 subunit is inactive but contributes to the structuring of the Rrp41 active site. The high sequence similarity of this archaeal exosome to eukaryotic exosomes and its high structural similarity to the bacterial mRNA–degrading PNPase support a common basis for RNA-degrading machineries in all three domains of life.

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Figure 1: Structural similarity of the S. solfataricus Rrp41 and Rrp42 exosome components with bacterial exoribonucleases.
Figure 2: Structure of the RNase PH ring of the S. solfataricus exosome.
Figure 3: Identification of the S. solfataricus exosomal activity within Rrp41.
Figure 4: Conserved molecular interactions and surfaces of the exosomal core.
Figure 5: Comparison of archaeal and eukaryotic exosomes.

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Acknowledgements

We thank M. Jinek and F. Glavan as well as the staff at the Swiss Light Source for data collection. We also thank P. Brick, E. Izaurralde, M. Sattler, A. Cook, M. Jinek and M. Hothorn for many valuable discussions and for critical reading of the manuscript. We thank G. Schuster for sharing unpublished data. This work was supported by the Deutsche Forschungsgemeinschaft and by the European 6th Framework Programme. E.L. was supported by the Danish Natural Science Research Council. P.W. was supported by a fellowship by Fonds der Chemischen Industrie.

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Correspondence to Elena Conti.

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Supplementary information

Supplementary Fig. 1

Reconstitution of the archaeal exosome RNase PH core complex. (PDF 1504 kb)

Supplementary Fig. 2

Complete structure-based sequence alignment with human homologs. (PDF 5670 kb)

Supplementary Fig. 3

Surface conservation of the exosome core. (PDF 3304 kb)

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Lorentzen, E., Walter, P., Fribourg, S. et al. The archaeal exosome core is a hexameric ring structure with three catalytic subunits. Nat Struct Mol Biol 12, 575–581 (2005). https://doi.org/10.1038/nsmb952

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