The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation
Posted on 2019-10-23 - 08:26
Abstract 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.
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Hildebrandt, Andrea; Brüggemann, Mirko; Rücklé, Cornelia; Boerner, Susan; Heidelberger, Jan; Busch, Anke; et al. (2019). The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4708787.v1
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AUTHORS (18)
AH
Andrea Hildebrandt
MB
Mirko Brüggemann
CR
Cornelia Rücklé
SB
Susan Boerner
JH
Jan Heidelberger
AB
Anke Busch
HH
Heike Hänel
AV
Andrea Voigt
MM
Martin Möckel
SE
Stefanie Ebersberger
AS
Anica Scholz
AD
Annabelle Dold
TS
Tobias Schmid
IE
Ingo Ebersberger
JR
Jean-Yves Roignant
KZ
Kathi Zarnack
JK
Julian König
PB
Petra Beli