The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs

Nature Communications
Aitor GarziaNahum Sonenberg

Abstract

Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the molecular sensors of aberrant mRNAs and their mechanism of action remain unknown. We studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating ribosomes. Cross-linked reads originating from AAA-decoding tRNALys(UUU) were 10-fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA) induced RQC in a ZNF598-dependent manner. Encounter with translated polyA segments by ZNF598 triggered ubiquitination of several ribosomal proteins, requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA tails by a specialized RNA-binding protein is a novel nucleic-acid-based surveillance mechanism of RQC.

References

Oct 3, 1999·Nature Genetics·S Laberge-le CouteulxE Tournier-Lasserve
Mar 4, 2000·Nature Genetics·S A GaytherC Caldas
Sep 28, 2000·Cell·Claudio A P Joazeiro, A M Weissman
May 19, 2001·Genes & Development·T LudwigA Efstratiadis
Sep 30, 2008·Journal of Molecular Biology·Jianli Lu, Carol Deutsch
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jessie ChuSteve A Kay
Feb 11, 2009·The Journal of Biological Chemistry·Lyudmila N DimitrovaToshifumi Inada
Mar 28, 2009·Nature·Steven Bergink, Stefan Jentsch
Jun 6, 2009·Annual Review of Biochemistry·Raymond J Deshaies, Claudio A P Joazeiro
Aug 29, 2009·Science·Wei-Lei YangHui-Kuan Lin
Jan 13, 2010·Molecular Cell·J Ross Buchan, Roy Parker
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Mar 4, 2010·Genome Biology·Mark D Robinson, Alicia Oshlack
Jul 20, 2010·Nature Biotechnology·Guoqiang XuSamie R Jaffrey
Oct 1, 2010·Nature·Daisuke KaidaGideon Dreyfuss
May 20, 2011·Nature·Björn SchwanhäusserMatthias Selbach
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Jul 4, 2012·Molecular and Cellular Biology·Masahiro MoritaNahum Sonenberg
Jul 19, 2012·Biochemistry. Biokhimii︠a︡·S V RazinO L Kantidze
May 3, 2013·Nature·Andreas M AngerR Beckmann
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Oct 31, 2013·Methods in Molecular Biology·Punto Bawono, Jaap Heringa
Nov 14, 2014·Bioinformatics·David T Jones, Domenico Cozzetto
Apr 23, 2015·Nature·Heena KhatterBruno P Klaholz
Sep 1, 2015·Science Advances·Laura ArthurSergej Djuranovic
Oct 8, 2015·Annual Review of Cell and Developmental Biology·Zhen Shi, Maria Barna
Jan 7, 2016·Nature Structural & Molecular Biology·Onn Brandman, Ramanujan S Hegde
Jun 28, 2016·Nature Methods·Stefka TyanovaJürgen Cox
Oct 23, 2016·Methods : a Companion to Methods in Enzymology·Aitor GarziaThomas Tuschl

Citations

Jan 10, 2018·Cold Spring Harbor Perspectives in Biology·Adam M Heck, Jeffrey Wilusz
Oct 31, 2017·Nature Structural & Molecular Biology·Anshuk SarkarEd Hurt
Feb 8, 2018·ELife·Seyed Mehdi JafarnejadNahum Sonenberg
Nov 2, 2018·Wiley Interdisciplinary Reviews. RNA·Nathan MeadeDerek Walsh
Jun 21, 2019·ELife·Karole N D'OrazioRachel Green
Aug 24, 2019·Genes & Development·Daniel PeterElisa Izaurralde
Nov 29, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Pankaj ThapaWojciech Pokrzywa
Jan 18, 2020·Nucleic Acids Research·Toshifumi Inada
Mar 24, 2020·Nature Structural & Molecular Biology·Yoshitaka MatsuoToshifumi Inada
Apr 25, 2020·The Journal of Cell Biology·Dan Li, Jianlong Wang
May 30, 2020·ELife·Slavica Pavlovic DjuranovicSergej Djuranovic
Jun 23, 2020·Annual Review of Biochemistry·Cole S Sitron, Onn Brandman
May 30, 2020·Journal of Cell Science·Stephen DiGiuseppeDerek Walsh
Mar 16, 2018·Molecular Biology of the Cell·Nathan ZuzowEric J Bennett
Feb 6, 2019·Nature Communications·Marie-Luise WinzDavid Tollervey
Apr 4, 2019·Nature Reviews. Molecular Cell Biology·Claudio A P Joazeiro
May 5, 2018·Nature Reviews. Genetics·Naomi R Genuth, Maria Barna
Feb 2, 2019·Frontiers in Genetics·Ken IkeuchiToshifumi Inada
Nov 27, 2019·Nature Structural & Molecular Biology·Viswanathan ChandrasekaranRamanujan S Hegde
Feb 14, 2020·International Journal of Molecular Sciences·Shannon E DoughertyGustavo M Silva
Jul 11, 2018·Biochemical Society Transactions·Huili Guo
Aug 17, 2020·The Biochemical Journal·Rodrigo D RequiãoFernando L Palhano
Feb 13, 2020·Proceedings of the National Academy of Sciences of the United States of America·Débora Broch TrentiniF Ulrich Hartl
Feb 11, 2020·Frontiers in Cell and Developmental Biology·Carsten J BeeseLisa B Frankel
Oct 13, 2020·Current Genetics·Sezen Meydan, Nicholas R Guydosh
Nov 29, 2020·Journal of Cell Science·Ben P Phillips, Elizabeth A Miller
Aug 15, 2019·Cell Reports·Carrie L SimmsHani S Zaher
Jul 21, 2020·Current Opinion in Structural Biology·Kyle T PowersChristiane Schaffitzel
Jan 29, 2021·The Journal of Cell Biology·Anne ClancyMichael J Clague
Oct 30, 2020·Cells·Anna Vainshtein, Paolo Grumati
Apr 3, 2020·Cell Reports·Marissa L GloverJoshua A Arribere
Feb 2, 2020·Molecular Cell·Alexandra ZinovievTatyana V Pestova
Jul 3, 2020·Molecular Cell·Sezen Meydan, Nicholas R Guydosh
Mar 14, 2021·Molecular Cell·Karole N D'Orazio, Rachel Green
Apr 29, 2021·Molecular Cell·Anna ThrunClaudio A P Joazeiro
May 1, 2021·International Journal of Molecular Sciences·Sara Martín-VillanuevaJesús de la Cruz
May 1, 2021·Biochimie·Esben M Quistgaard
May 6, 2021·Wiley Interdisciplinary Reviews. RNA·Christelle MorrisEmiliano P Ricci
May 10, 2021·Trends in Biochemical Sciences·Matthew C J Yip, Sichen Shao
May 12, 2021·Cellular Signalling·Lilas AlboushiSeyed Mehdi Jafarnejad
May 22, 2021·Nature Communications·Fiorella GhisaysJohn H J Petrini
Jun 6, 2021·Cell Chemical Biology·Robert S MaginSara J Buhrlage

Datasets Mentioned

BETA
SRR5137268
SRR5137269

Methods Mentioned

BETA
ubiquitination
immunoprecipitation
protein-folding
transfection
PCR
flow cytometry
BioShop
Gel Filtration
PAR-CLIP

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