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

细胞分裂中 RNA 依赖性蛋白质图谱揭示有丝分裂蛋白质-蛋白质相互作用的核糖体调节

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作者:Varshni Rajagopal, Jeanette Seiler, Isha Nasa, Simona Cantarella, Jana Theiss, Franziska Herget, Bianca Kaifer, Martin Schneider, Dominic Helm, Julian König, Kathi Zarnack, Sven Diederichs, Arminja N Kettenbach, Maïwen Caudron-Herger

Abstract

Ribonucleoprotein complexes are dynamic assemblies of RNA with RNA-binding proteins (RBPs), which can modulate the fate of the RNA molecules from transcription to degradation. Vice versa, RNA can regulate the interactions and functions of the associated proteins. Dysregulation of RBPs is linked to diseases such as cancer and neurological disorders. RNA and RBPs are present in mitotic structures like the centrosomes and spindle microtubules, but their influence on mitotic spindle integrity remains unknown. Thus, we applied the R-DeeP strategy for the proteome-wide identification of RNA-dependent proteins and complexes to cells synchronized in mitosis versus interphase. The resulting atlas of RNA-dependent proteins in cell division can be accessed through the R-DeeP 3.0 database (R-DeeP3.dkfz.de). It revealed key mitotic factors as RNA-dependent such as AURKA, KIFC1 and TPX2 that were linked to RNA despite their lack of canonical RNA-binding domains. KIFC1 was identified as a new interaction partner and phosphorylation substrate of AURKA at S349 and T359. In addition, KIFC1 interacted with both, AURKA and TPX2, in an RNA-dependent manner. Our data suggest a riboregulation of mitotic protein-protein interactions during spindle assembly, offering new perspectives on the control of cell division processes by RNA-protein complexes.

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