The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation.
The exosome is a conserved macromolecular complex essential for RNA degradation. The nine-subunit core of the eukaryotic exosome shares a similar barrel-like architecture with prokaryotic complexes, but is catalytically inert. Here, we investigate how the Rrp44 nuclease functions in the active ten-subunit exosome. The 3.0 A resolution crystal structure of the yeast Rrp44-Rrp41-Rrp45 complex shows how the nuclease interacts with the exosome core and the relative accessibility of its endoribonuclease and exoribonuclease sites. Biochemical studies indicate that RNAs thread through the central channel of the core to reach the Rrp44 exoribonuclease site. This channeling mechanism involves evolutionary conserved residues. It allows the processive unwinding and degradation of RNA duplexes containing a sufficiently long single-stranded 3' extension, without the requirement for helicase activities. Although the catalytic function of the exosome core has been lost during evolution, the substrate recruitment and binding properties have been conserved from prokaryotes to eukaryotes.
Bonneau
Fabien
F
Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Basquin
Jérôme
J
Ebert
Judith
J
Lorentzen
Esben
E
Conti
Elena
E
D063326:Exosome Multienzyme Ribonuclease Complex; D055354:Exosomes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D012313:RNA / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D063326:Exosome Multienzyme Ribonuclease Complex; C542283:DIS3 protein, S cerevisiae