The Human SKI Complex Regulates Channeling of Ribosome-bound RNA to the Exosome Via an Intrinsic Gatekeeping Mechanism

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2022 Feb 5

PMID 35120588

Authors

Alexander Kogel

Achim Keidel

Fabien Bonneau

Ingmar B Schafer

Elena Conti

Affiliations

Soon will be listed here.

Abstract

The superkiller (SKI) complex is the cytoplasmic co-factor and regulator of the RNA-degrading exosome. In human cells, the SKI complex functions mainly in co-translational surveillance-decay pathways, and its malfunction is linked to a severe congenital disorder, the trichohepatoenteric syndrome. To obtain insights into the molecular mechanisms regulating the human SKI (hSKI) complex, we structurally characterized several of its functional states in the context of 80S ribosomes and substrate RNA. In a prehydrolytic ATP form, the hSKI complex exhibits a closed conformation with an inherent gating system that effectively traps the 80S-bound RNA into the hSKI2 helicase subunit. When active, hSKI switches to an open conformation in which the gating is released and the RNA 3' end exits the helicase. The emerging picture is that the gatekeeping mechanism and architectural remodeling of hSKI underpin a regulated RNA channeling system that is mechanistically conserved among the cytoplasmic and nuclear helicase-exosome complexes.

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