Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex

Nature, 2013, doi:10.1038/nature11870, 495, 70–75 published on 03.02.2013
Nature, online article
The exosome is the major 3′–5′ RNA-degradation complex in eukaryotes. The ubiquitous core of the yeast exosome (Exo-10) is formed by nine catalytically inert subunits (Exo-9) and a single active RNase, Rrp44. In the nucleus, the Exo-10 core recruits another nuclease, Rrp6. Here we crystallized an approximately 440-kilodalton complex of Saccharomyces cerevisiae Exo-10 bound to a carboxy-terminal region of Rrp6 and to an RNA duplex with a 3′-overhang of 31 ribonucleotides. The 2.8 Å resolution structure shows how RNA is funnelled into the Exo-9 channel in a single-stranded conformation by an unwinding pore. Rrp44 adopts a closed conformation and captures the RNA 3′-end that exits from the side of Exo-9. Exo-9 subunits bind RNA with sequence-unspecific interactions reminiscent of archaeal exosomes. The substrate binding and channelling mechanisms of 3′–5′ RNA degradation complexes are conserved in all kingdoms of life.

TU München
Helmholtz München
MPI of Neurobiology
MPI of Biochemistry