The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity

Cell. 2017 Jun 1;169(6):1051-1065.e18. doi: 10.1016/j.cell.2017.05.022.


During eukaryotic evolution, ribosomes have considerably increased in size, forming a surface-exposed ribosomal RNA (rRNA) shell of unknown function, which may create an interface for yet uncharacterized interacting proteins. To investigate such protein interactions, we establish a ribosome affinity purification method that unexpectedly identifies hundreds of ribosome-associated proteins (RAPs) from categories including metabolism and cell cycle, as well as RNA- and protein-modifying enzymes that functionally diversify mammalian ribosomes. By further characterizing RAPs, we discover the presence of ufmylation, a metazoan-specific post-translational modification (PTM), on ribosomes and define its direct substrates. Moreover, we show that the metabolic enzyme, pyruvate kinase muscle (PKM), interacts with sub-pools of endoplasmic reticulum (ER)-associated ribosomes, exerting a non-canonical function as an RNA-binding protein in the translation of ER-destined mRNAs. Therefore, RAPs interconnect one of life's most ancient molecular machines with diverse cellular processes, providing an additional layer of regulatory potential to protein expression.

Keywords: PKM; RNA-binding proteins; endoplasmic reticulum; metabolism; ribosome; ribosome heterogeneity; translation; ufmylation.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Embryonic Stem Cells / metabolism
  • Endoplasmic Reticulum / metabolism
  • Mass Spectrometry
  • Membrane Proteins / metabolism
  • Mice
  • Protein Biosynthesis
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational
  • Ribosomal Proteins / metabolism
  • Ribosomes / chemistry*
  • Ribosomes / metabolism*
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / metabolism
  • Ubiquitin-Protein Ligases / metabolism


  • Carrier Proteins
  • Membrane Proteins
  • Ribosomal Proteins
  • Thyroid Hormones
  • UFL1 protein, mouse
  • Ubiquitin-Protein Ligases