An atlas of RNA-dependent proteins in cell division reveals the riboregulation of mitotic protein-protein interactions

Abstract

Abstract Ribonucleoprotein complexes are dynamic assemblies of RNA with RNA-binding proteins, which modulate the fate of RNA. Inversely, RNA riboregulates the interactions and functions of the associated proteins. Dysregulation of ribonucleoprotein functions is linked to diseases such as cancer and neurological disorders. In dividing cells, RNA and RNA-binding proteins are present in mitotic structures, but their impact on cell division remains unclear. By applying the proteome-wide R-DeeP strategy to cells synchronized in mitosis versus interphase integrated with the RBP2GO knowledge, we provided an atlas of RNA-dependent proteins in cell division, accessible at R-DeeP3.dkfz.de. We uncovered AURKA, KIFC1 and TPX2 as unconventional RNA-binding proteins. KIFC1 was identified as a new substrate of AURKA, and new TPX2-interacting protein. Their pair-wise interactions were RNA dependent. In addition, RNA stimulated AURKA kinase activity and stabilized its conformation. In this work, we highlighted riboregulation of major mitotic factors as an additional complexity level of cell division.