Cell
Volume 169, Issue 6, 1 June 2017, Pages 1051-1065.e18
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Article
The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity

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Highlights

  • A mammalian ribosome affinity approach reveals ribosome-associated proteins (RAPs)

  • A multitude of RAPs link the ribosome to diverse cellular and molecular functions

  • Ribosomes are modified by metazoan-specific ufmylation

  • A metabolic enzyme, PKM, is at ER ribosomes and translates ER-destined mRNAs

Summary

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

ribosome
translation
RNA-binding proteins
metabolism
ufmylation
PKM
ribosome heterogeneity
endoplasmic reticulum

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