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The Rqc2/Tae2 subunit of the ribosome-associated quality control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation

Authors :
Ryo Yonashiro
Erich B Tahara
Mario H Bengtson
Maria Khokhrina
Holger Lorenz
Kai-Chun Chen
Yu Kigoshi-Tansho
Jeffrey N Savas
John R Yates III
Steve A Kay
Elizabeth A Craig
Axel Mogk
Bernd Bukau
Claudio AP Joazeiro
Source :
eLife, Vol 5 (2016)
Publication Year :
2016
Publisher :
eLife Sciences Publications Ltd, 2016.

Abstract

Ribosome stalling during translation can potentially be harmful, and is surveyed by a conserved quality control pathway that targets the associated mRNA and nascent polypeptide chain (NC). In this pathway, the ribosome-associated quality control (RQC) complex promotes the ubiquitylation and degradation of NCs remaining stalled in the 60S subunit. NC stalling is recognized by the Rqc2/Tae2 RQC subunit, which also stabilizes binding of the E3 ligase, Listerin/Ltn1. Additionally, Rqc2 modifies stalled NCs with a carboxy-terminal, Ala- and Thr-containing extension—the 'CAT tail'. However, the function of CAT tails and fate of CAT tail-modified ('CATylated') NCs has remained unknown. Here we show that CATylation mediates formation of detergent-insoluble NC aggregates. CATylation and aggregation of NCs could be observed either by inactivating Ltn1 or by analyzing NCs with limited ubiquitylation potential, suggesting that inefficient targeting by Ltn1 favors the Rqc2-mediated reaction. These findings uncover a translational stalling-dependent protein aggregation mechanism, and provide evidence that proteins can become specifically marked for aggregation.

Details

Language :
English
ISSN :
2050084X
Volume :
5
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.5ceb291f38b646cd975c66eb50299b36
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.11794