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PreprintCited by 15RNA and protein synthesis mechanismsAdvanced Proteomics Techniques and ApplicationsRNA modifications and cancer

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Proteomics-based characterization of ribosome heterogeneity in adult mouse organs

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Brunchault, Marie R, Hesse, Anne-Marie, Schaeffer, Julia, Decourt, Charlotte, Combes, Florence, Nawabi, Homaira, Couté, Yohann, Belin, Stephane·2024·Cellular and Molecular Life Sciences
DOI 10.1101/2024.02.23.581691PMC PMC12022211

Preprint — published as 10.1007/s00018-025-05708-7

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Abstract

While long thought to be invariable in all cellular organisms, evidence has emerged that the translation process, i.e. protein assembly from mRNA sequence decoding, is regulated by variable features of the translation machinery. Notably, ribosomes, the functional units of protein synthesis, display variations in their composition, depending on the developmental stage, cell type or physiopathological context, thus providing a new level of actionable regulation of gene expression. Yet, a comprehensive map of the heterogeneity of ribosome composition in ribosomal proteins (RPs) in different organs and tissues is not available. In this work, we explored tissue-specific ribosome heterogeneity using mass spectrometry-based quantitative proteomic characterization of ribosomal fractions purified from 14 adult mouse organs and tissues. We performed crossed clustering and statistical analyses of RP composition to highlight stable, variable and tissue-specific RPs across organs and tissues. Focusing on specific RPs, we validated their relative abundance with a targeted proteomic approach, which gave further insight into the tissue-specific ribosome RP signature. Finally, we investigated the origin of RP variations in ribosome fraction of the different tissues, by comparing RP relative abundances in our proteomic dataset and in three independent transcriptomic datasets. Interestingly, we found that, in some tissues, the RP abundance in purified ribosomes does not always correlate with the corresponding RP transcript level, arguing for a translational regulation of RP expression, and/or a regulated incorporation of RPs into ribosomes. Altogether, our data support the notion of a tissue-specific RP signature of ribosomes, which opens avenues to study how specific ribosomal composition provides an additional level of regulation to control gene expression in different tissues and organs.

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Metadata

Authors
Brunchault, M. R., Hesse, A.-M., Schaeffer, J., Decourt, C., Combes, F., Nawabi, H., Couté, Y., & Belin, S.
Affiliations
  • Inserm (FR)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Couté, Yohann
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
openRxiv
Published
2024-02-24
Volume
82
Issue
1
Pages
175-175
ISSN
1420-682X (ISSN-L)
DOI
10.1101/2024.02.23.581691
PMC
PMC12022211
OpenAlex
W4409763838
Cited by
15
References
1
Citations by year
2026: 8 · 2025: 6 · 2024: 1
FWCI
4.18
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cellular and Molecular Life Sciences (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
Funders
  • Agence Nationale de la Recherche (ANR-10-INBS-0008, ANR-10-INBS-08, ANR-17-EURE-0003, ANR-17-EURE-, 10-INBS-08, ANR18, ANR-18-CE16-0007, ANR-17, ANR-10)
  • Fondation pour la Recherche Médicale (ANR-17-EURE-0003, SPF201909009106)
  • European Research Council (ERC-St17-759089)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
ribosome heterogeneity, ribosomal proteins, translational regulation, mRNA levels, mouse organs, gene expression regulation
MeSH terms
Animals, Male, Mice, Inbred C57BL, Organ Specificity, Ribosomal Proteins, Ribosomes, Mass Spectrometry, Protein Biosynthesis, Proteome, Proteomics, Mice

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