The RNA-binding Ubiquitin Ligase MKRN1 Functions in Ribosome-Associated Quality Control of poly(A) Translation

Genome Biol. 2019 Oct 22;20(1):216. doi: 10.1186/s13059-019-1814-0.


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.

Keywords: MKRN1; Poly(A); RNA binding; Ribosome-associated quality control; Translation; Ubiquitin remnant profiling; Ubiquitylation; iCLIP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • HEK293 Cells
  • Humans
  • Nerve Tissue Proteins / metabolism*
  • Poly(A)-Binding Protein I / metabolism
  • Protein Biosynthesis*
  • RNA, Messenger / metabolism
  • Ribonucleoproteins / metabolism*
  • Ubiquitination


  • 3' Untranslated Regions
  • Makorin ring finger protein 1
  • Nerve Tissue Proteins
  • Poly(A)-Binding Protein I
  • RNA, Messenger
  • Ribonucleoproteins