The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation
Related Experiment Video
Updated: Jan 5, 2026
Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
Published on: October 28, 2014
Andrea Hildebrandt1, Mirko Brüggemann2, Cornelia Rücklé1,2
1Institute of Molecular Biology (IMB), Ackermannweg 4, 55128, Mainz, Germany.
Background:
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.
Results:
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.
Conclusions:
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.
Insights
The E3 ubiquitin ligase MKRN1 stalls ribosomes at poly(A) sequences, preventing aberrant protein production. This mechanism maintains proteome integrity by degrading faulty transcripts via ribosome-associated quality control.
Area of Science:
- Molecular Biology
- Cell Biology
- Protein Homeostasis
Background:
- Cells utilize quality control to degrade aberrant mRNAs and proteins, maintaining protein homeostasis.
- Premature polyadenylation of mRNAs can lead to non-functional proteins.
- Ribosome stalling at poly(A) sequences triggers degradation of truncated polypeptides via ribosome-associated quality control.
Purpose of the Study:
- To investigate the role of the RNA-binding E3 ubiquitin ligase MKRN1 in ribosome-associated quality control.
- To elucidate the mechanism by which MKRN1 recognizes and processes aberrant mRNAs.
Main Methods:
- Direct binding assays between MKRN1 and PABPC1.
- Polysome association studies.
- Ubiquitin remnant profiling.
- In vitro ubiquitylation assays.
Main Results:
- MKRN1 promotes ribosome stalling at poly(A) sequences.
- MKRN1 directly binds to PABPC1 and associates with polysomes.
- MKRN1 ubiquitinates PABPC1 and ribosomal protein RPS10.
Conclusions:
- MKRN1 recognizes poly(A) tails, preventing the synthesis of erroneous proteins from prematurely polyadenylated transcripts.
- MKRN1 plays a crucial role in maintaining proteome integrity through ribosome-associated quality control.
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