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

Ryo YonashiroClaudio A P Joazeiro


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.


Dec 1, 1994·Nature·D A ParsellSusan Lindquist
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·P Lopez-BuesaElizabeth A Craig
Oct 19, 1999·Molecular and Cellular Biology·W Yan, Elizabeth A Craig
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·S Krobitsch, Susan Lindquist
May 27, 2005·Current Opinion in Genetics & Development·Andrea Albrecht, Stefan Mundlos
Jul 31, 2007·Genetics·Marenda A WilsonAmbro van Hoof
Apr 23, 2008·Current Protocols in Bioinformatics·Daniel CociorvaJohn R Yates
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jessie ChuSteve A Kay
Apr 7, 2010·The Journal of Cell Biology·Ansgar KoplinElke Deuerling
Sep 14, 2010·Nature·Mario H Bengtson, Claudio A P Joazeiro
Apr 5, 2011·Annual Review of Biochemistry·Brandon H Toyama, Jonathan S Weissman
Aug 11, 2012·Genetics·Susan W Liebman, Yury O Chernoff
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Mar 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Quentin DefenouillèreMicheline Fromont-Racine
Aug 21, 2013·Journal of Proteomics·Sophie A ComynThibault Mayor
Feb 19, 2014·The Journal of Cell Biology·Jens Lykke-Andersen, Eric J Bennett
Oct 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Dmitry LyumkisClaudio A P Joazeiro
Jan 13, 2015·Molecular Cell·Sichen ShaoRamanujan S Hegde
Feb 24, 2015·Biochimie·Feng WangJon M Huibregtse
Jun 5, 2015·Frontiers in Molecular Biosciences·Axel MogkBernd Bukau
Aug 8, 2015·Nature·Nadinath B NillegodaBernd Bukau


Jul 8, 2016·Proceedings of the National Academy of Sciences of the United States of America·Selom K DoamekporClaudio A P Joazeiro
Jan 21, 2017·Nature Communications·Laura L ArthurSergej Djuranovic
Apr 26, 2017·Annual Review of Biochemistry·F Ulrich Hartl
May 11, 2017·Annual Review of Biochemistry·Emily Mitchell SontagJudith Frydman
Oct 31, 2017·PLoS Genetics·Brenda A SchilkeElizabeth A Craig
Jun 6, 2018·Wiley Interdisciplinary Reviews. RNA·Laura L Arthur, Sergej Djuranovic
Nov 21, 2018·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration
Dec 7, 2018·The Journal of Biological Chemistry·Kevin C Stein, Judith Frydman
Mar 3, 2018·Scientific Reports·Nur Hidayah JamarChris M Grant
Jul 2, 2016·Science·David BalchinF Ulrich Hartl
Sep 16, 2016·Nature·J Wade Harper, Eric J Bennett
May 28, 2019·Nature Structural & Molecular Biology·Cole S Sitron, Onn Brandman
Apr 25, 2020·The Journal of Cell Biology·Dan Li, Jianlong Wang
May 20, 2016·Wiley Interdisciplinary Reviews. RNA·Carrie L SimmsHani S Zaher
Jun 23, 2020·Annual Review of Biochemistry·Cole S Sitron, Onn Brandman
Feb 15, 2017·RNA·Nicholas R Guydosh, Rachel Green
Mar 16, 2018·Molecular Biology of the Cell·Nathan ZuzowEric J Bennett
Jul 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Alexandra N MarshallAmbro van Hoof
Feb 9, 2019·Nature Reviews. Molecular Cell Biology·Mark S HippF Ulrich Hartl
Mar 6, 2019·Cold Spring Harbor Perspectives in Biology·Gopal G JayarajF Ulrich Hartl
Apr 4, 2019·Nature Reviews. Molecular Cell Biology·Claudio A P Joazeiro
Sep 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Shuangxi LiBingwei Lu
Oct 17, 2016·Essays in Biochemistry·Martin Gamerdinger
Jul 19, 2017·Annual Review of Cell and Developmental Biology·Claudio A P Joazeiro
Feb 6, 2019·Nature Communications·Marie-Luise WinzDavid Tollervey
Feb 2, 2019·Frontiers in Genetics·Ken IkeuchiToshifumi Inada
Aug 1, 2017·Nature Communications·Yoshitaka MatsuoToshifumi Inada
Nov 27, 2019·Nature Structural & Molecular Biology·Viswanathan ChandrasekaranRamanujan S Hegde
Jun 21, 2020·Nature Communications·Yeonkyoung ParkYoon Ki Kim
Sep 24, 2020·International Journal of Molecular Sciences·Mafalda Escobar-Henriques, Vincent Anton
Aug 17, 2020·The Biochemical Journal·Rodrigo D RequiãoFernando L Palhano
May 22, 2017·Current Genetics·Quentin Defenouillère, Micheline Fromont-Racine
Apr 24, 2019·Nature Structural & Molecular Biology·Matthew C J YipSichen Shao
Jun 8, 2018·Nature Communications·Olga Zurita RendónJared Rutter
Apr 12, 2017·Frontiers in Molecular Neuroscience·Simon AlbertiSerena Carra
Oct 13, 2020·Current Genetics·Sezen Meydan, Nicholas R Guydosh

Methods Mentioned

fluorescence microscopy
pull down
affinity purification

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