Structures and Functions of the Ribosome Quality control Complex or RQC

Abstract

In this talk I will present new structural and functional data concerning the roles and mechanisms of the RQC in cotranslational protein quality control. I will present new cryo‐EM reconstructions and a complete in vitro reconstitution system that sheds new light on how Rqc2 catalyzes the synthesis of Carboxy‐terminal Alanine and Threonine tails or “CAT tails”, and how CAT tailing differs from the canonical chemistry of translation. I will also describe how CAT tail elongation facilitates ubiquitination of failed nascent chains by the E3 ubiquitin ligase, Ltn1, as well as the still poorly characterized RQC component, Rqc1. Our new data demonstrates that CAT tailing by Rqc2 exposes previously inaccessible ubiquitin acceptors to the RING domain of Ltn1 for ubiquitination. CAT tailing, moreover, promotes hydrolytic release of nascent chains from the tRNA molecules in the P‐site of of the 60S subunit, and CAT tails are necessary for nascent chain degradation off certain substrates in vivo.Support or Funding InformationNIH DP2 1DP2GM110772‐01Howard Hughes Medical Institute Faculty Scholar AwardSandler Family Foundation, Program for Breakthrough Biomedical Research