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The RNA-binding protein landscapes differ between mammalian organs and cultured cells

View ORCID ProfileJoel I. Perez-Perri, View ORCID ProfileDunja Ferring-Appel, View ORCID ProfileIna Huppertz, View ORCID ProfileThomas Schwarzl, View ORCID ProfileFrank Stein, View ORCID ProfileMandy Rettel, View ORCID ProfileBruno Galy, View ORCID ProfileMatthias W. Hentze
doi: https://doi.org/10.1101/2022.02.10.479897
Joel I. Perez-Perri
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
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Dunja Ferring-Appel
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
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  • ORCID record for Dunja Ferring-Appel
Ina Huppertz
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
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Thomas Schwarzl
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
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Frank Stein
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
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Mandy Rettel
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
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Bruno Galy
2German Cancer Research Center (DKFZ), Division of Virus-associated Carcinogenesis, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
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  • For correspondence: b.galy@dkfz.de hentze@embl.org
Matthias W. Hentze
1European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
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  • For correspondence: b.galy@dkfz.de hentze@embl.org
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Summary

System-wide approaches have unveiled an unexpected breadth of the RNA-bound proteomes of cultured cells. Corresponding information regarding RNA-binding proteins (RBPs) of mammalian organs is still missing, largely due to technical challenges. Here, we describe ex vivo eRIC (enhanced RNA interactome capture) to characterize the poly(A)RNA-bound proteomes of three different mouse organs. The resulting organ atlases encompass more than 1300 RBPs active in brain, kidney or liver. Nearly a quarter (291) of these had formerly not been identified in cultured cells, with more than 100 being metabolic enzymes. Remarkably, RBP activity differs between organs independent of RBP abundance, suggesting organ-specific levels of control. Similarly, we identify systematic differences in RNA binding between animal organs and cultured cells. The pervasive RNA binding of enzymes of intermediary metabolism in organs points to tightly knit connections between gene expression and metabolism, and displays a particular enrichment for enzymes that use nucleotide cofactors. We describe a generically applicable refinement of the eRIC technology and provide an instructive resource of RBPs active in intact mammalian organs, including the brain.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 10, 2022.
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The RNA-binding protein landscapes differ between mammalian organs and cultured cells
Joel I. Perez-Perri, Dunja Ferring-Appel, Ina Huppertz, Thomas Schwarzl, Frank Stein, Mandy Rettel, Bruno Galy, Matthias W. Hentze
bioRxiv 2022.02.10.479897; doi: https://doi.org/10.1101/2022.02.10.479897
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The RNA-binding protein landscapes differ between mammalian organs and cultured cells
Joel I. Perez-Perri, Dunja Ferring-Appel, Ina Huppertz, Thomas Schwarzl, Frank Stein, Mandy Rettel, Bruno Galy, Matthias W. Hentze
bioRxiv 2022.02.10.479897; doi: https://doi.org/10.1101/2022.02.10.479897

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