Cited by 448RNA and protein synthesis mechanismsRNA modifications and cancerRNA Research and Splicing

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The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity

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Simsek, Deniz, Tiu, Gerald C., Flynn, Ryan A., Byeon, Gun W., Leppek, Kathrin, Xu, Adele F., Chang, Howard Y., Barna, Maria·2017·Cell

DOI 10.1016/j.cell.2017.05.022PMC PMC5548193

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Abstract

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.

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Additional file 3 of A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation
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Additional file 8 of A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation
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Additional file 6 of A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation
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Additional file 2 of A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation
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Additional file 4 of A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation
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Additional file 10 of A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation
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Additional file 7 of A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation
Ren, Y., Huo, Y., Li, W., He, M., Liu, S., Yang, J., Zhao, H., Xu, L., Guo, Y., Si, Y., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16815567

Authors: Simsek, D., Tiu, G. C., Flynn, R. A., Byeon, G. W., Leppek, K., Xu, A. F., Chang, H. Y., & Barna, M.
Affiliations: Stanford University (US)
Stanford Medicine (US)
Corresponding author: Barna, Maria
ORCID: Simsek, Deniz
Tiu, Gerald C.
Flynn, Ryan A.
Byeon, Gun W.
Leppek, Kathrin
Xu, Adele F.
Chang, Howard Y.
Barna, Maria
Venue: Cell
Publisher: Elsevier BV
Published: 2017-06
Volume: 169
Issue: 6
Pages: 1051-1065.e18
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2017.05.022
PMC: PMC5548193
OpenAlex: W2621126205
Cited by: 439
References: 74
Citations by year: 2026: 34 · 2025: 62 · 2024: 44 · 2023: 40 · 2022: 29 · 2021: 53 · 2020: 63 · 2019: 48 · 2018: 47 · 2017: 18
FWCI: 19.65
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: New York Stem Cell Foundation (NYSCF-R-I36)
NIH Director’s New Innovator Award (7DP2OD008509, R21HD086730)
Alfred P. Sloan Research Fellowship (BR2014)
Mallinckrodt Foundation Award
Pew Scholars Award (P50-HG007735, R01-HG004361, R01-ES023168)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords: ribosome-associated proteins, ribosome heterogeneity, UFMylation, post-translational modification, RNA-binding proteins
MeSH terms: Thyroid Hormone-Binding Proteins, Animals, Carrier Proteins, Endoplasmic Reticulum, Membrane Proteins, Protein Processing, Post-Translational, Ribosomal Proteins, Ribosomes, Mass Spectrometry, Thyroid Hormones, Protein Biosynthesis, Protein Interaction Mapping, Ubiquitin-Protein Ligases, Mice, Embryonic Stem Cells

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The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity

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