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

Details

Serval ID
serval:BIB_35684127C4F1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation.
Journal
Genome biology
Author(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
Publication state
Published
Issued date
22/10/2019
Peer-reviewed
Oui
Volume
20
Number
1
Pages
216
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
24/10/2019 16:12
Last modification date
04/01/2020 7:17
Usage data