The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation.

Détails

ID Serval
serval:BIB_35684127C4F1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation.
Périodique
Genome biology
Auteur(s)
Hildebrandt A., Brüggemann M., Rücklé C., Boerner S., Heidelberger J.B., Busch A., Hänel H., Voigt A., Möckel M.M., Ebersberger S., Scholz A., Dold A., Schmid T., Ebersberger I., Roignant J.Y., Zarnack K., König J., Beli P.
ISSN
1474-760X (Electronic)
ISSN-L
1474-7596
Statut éditorial
Publié
Date de publication
22/10/2019
Peer-reviewed
Oui
Volume
20
Numéro
1
Pages
216
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Cells have evolved quality control mechanisms to ensure protein homeostasis by detecting and degrading aberrant mRNAs and proteins. A common source of aberrant mRNAs is premature polyadenylation, which can result in non-functional protein products. Translating ribosomes that encounter poly(A) sequences are terminally stalled, followed by ribosome recycling and decay of the truncated nascent polypeptide via ribosome-associated quality control.
Here, we demonstrate that the conserved RNA-binding E3 ubiquitin ligase Makorin Ring Finger Protein 1 (MKRN1) promotes ribosome stalling at poly(A) sequences during ribosome-associated quality control. We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.
We propose that MKRN1 mediates the recognition of poly(A) tails to prevent the production of erroneous proteins from prematurely polyadenylated transcripts, thereby maintaining proteome integrity.
Mots-clé
3' Untranslated Regions, HEK293 Cells, Humans, Nerve Tissue Proteins/metabolism, Poly(A)-Binding Protein I/metabolism, Protein Biosynthesis, RNA, Messenger/metabolism, Ribonucleoproteins/metabolism, Ubiquitination, MKRN1, Poly(A), RNA binding, Ribosome-associated quality control, Translation, Ubiquitin remnant profiling, Ubiquitylation, iCLIP
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/10/2019 15:12
Dernière modification de la notice
04/01/2020 6:17
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