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

Joel I. Perez-Perri, Dunja Ferring-Appel, Ina Huppertz, Thomas Schwarzl, Sudeep Sahadevan, Frank Stein, Mandy Rettel, Bruno Galy () and Matthias W. Hentze ()
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Joel I. Perez-Perri: European Molecular Biology Laboratory
Dunja Ferring-Appel: European Molecular Biology Laboratory
Ina Huppertz: European Molecular Biology Laboratory
Thomas Schwarzl: European Molecular Biology Laboratory
Sudeep Sahadevan: European Molecular Biology Laboratory
Frank Stein: European Molecular Biology Laboratory
Mandy Rettel: European Molecular Biology Laboratory
Bruno Galy: Division of Virus-associated Carcinogenesis
Matthias W. Hentze: European Molecular Biology Laboratory

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract 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 enhanced RNA interactome capture (eRIC) to characterize the 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.

Date: 2023
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DOI: 10.1038/s41467-023-37494-w

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