Architecture of the yeast Rrp44–exosome complex suggests routes of RNA recruitment for 3′ end processing

Abstract

The eukaryotic core exosome (CE) is a conserved nine-subunit protein complex important for 3′ end trimming and degradation of RNA. In yeast, the Rrp44 protein constitutively associates with the CE and provides the sole source of processive 3′-to-5′ exoribonuclease activity. Here we present EM reconstructions of the core and Rrp44-bound exosome complexes. The two-lobed Rrp44 protein binds to the RNase PH domain side of the exosome and buttresses the bottom of the exosome-processing chamber. The Rrp44 C-terminal body part containing an RNase II-type active site is anchored to the exosome through a conserved set of interactions mainly to the Rrp45 and Rrp43 subunit, whereas the Rrp44 N-terminal head part is anchored to the Rrp41 subunit and may function as a roadblock to restrict access of RNA to the active site in the body region. The Rrp44–exosome (RE) architecture suggests an active site sequestration mechanism for strict control of 3′ exoribonuclease activity in the RE complex.