RT Journal Article SR Electronic T1 The RNA-binding protein landscapes differ between mammalian organs and cultured cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.02.10.479897 DO 10.1101/2022.02.10.479897 A1 Joel I. Perez-Perri A1 Dunja Ferring-Appel A1 Ina Huppertz A1 Thomas Schwarzl A1 Frank Stein A1 Mandy Rettel A1 Bruno Galy A1 Matthias W. Hentze YR 2022 UL http://biorxiv.org/content/early/2022/02/10/2022.02.10.479897.abstract AB 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 StatementThe authors have declared no competing interest.