Poring over exosome structure.

almost all rNa molecules are pro­ cessed by rNases to form mature rNas. in addition, many rNas are degraded, either because they are no longer needed or because they are aberrant. all of these functions—rNa processing, normal rNa degradation and rNa quality con­ trol—are carried out by the eukaryotic rNa exosome complex. in this issue of EMBO reports, the Lorentzen group provide struc­ tural insight into the eukaryotic exosome and the mechanism by which it degrades rNa from 3' to 5' (Malet et al, 2010). the crystal structures of overlapping parts of the eukaryotic exosome (Liu et al, 2006; Bonneau et al, 2009) and the related bacterial pNpase (Symmons et al, 2000) and archaeal exosome (Lorentzen et al, 2007) have been solved, and show that these rNa­degrading machines from the three domains of life have a similar structure (Fig 1). they are all composed of a ring of six rNase pH domains, one side of which has a cap that contains putative rNa­binding domains. although this overall structure is conserved, the way that it is formed is not. Bacterial pNpase is a homotrimer of which each mono mer contains two rNase pH domains, an S1 domain and a KH domain. the archaeal pH ring consists of three cop­ ies of two proteins and the cap is made of three copies of either one of two proteins. Finally, the eukaryotic exosome core is com­ posed of nine proteins: six with one rNase pH domain each and three cap proteins. in pNpase and the archaeal exosome, substrates enter the pH ring from the cap­ side. the putative rNa­binding domains of the cap are therefore probably important for controlling entry to the pH ring. in both archaea and bacteria, the active sites are on the inner side of the pH ring and thus the ribonucleic catalysis occurs inside the central channel. However, in humans and yeast each of the rNase pH domains have point mutations that make the exosome ring catalytically inactive (Dziembowski et al, 2007). instead, catalysis is carried out by a tenth subunit—rrp44/Dis3—which binds to the pH ring on the opposite side to the cap proteins (Bonneau et al, 2009; Wang et al, 2007). this organization made it unclear whether rNa also enters the central chan­ nel of the exosome in eukaryotes (Fig 1), or whether substrate rNas directly access the catalytic subunit. Malet and colleagues now provide struc­ tural information that resolves this by recon­ stituting the ten­subunit yeast exosome and analysing its structure with electron micro­ scopy, in the presence and absence of rNa. this analysis suggests that the rNase pH ring of the exosome is stable, but that the cap and catalytic subunits are more flexible than previously appreciated. it is the first structural evidence that in eukaryotes rNa is threaded through the central channel before being degraded by rrp44.