Ribeiro Diogo M, Prod'homme Alexis, Teixeira Adrien, Zanzoni Andreas, Brun Christine
Aix Marseille Univ, Inserm, TAGC, UMR_S1090, Marseille, France.
CNRS, Marseille, France.
Nucleic Acids Res. 2020 Jul 9;48(12):6491-6502. doi: 10.1093/nar/gkaa462.
Multifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3'UTRs were found to regulate the cellular localization of newly synthesized proteins through the formation of 3'UTR-protein complexes. Here, we investigate the formation of 3'UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human 'extreme multifunctional' (EMF) proteins, we predicted 1411 3'UTR-protein complexes involving 54% of those proteins and evaluated their role in regulating protein cellular localization and multifunctionality. We find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3'UTR-protein complexes, and that the formation of these complexes could provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Our findings are reinforced by archetypal moonlighting proteins predicted to form 3'UTR-protein complexes. Finally, the formation of 3'UTR-protein complexes that involves up to 17% of the proteins in the human protein-protein interaction network, may be a common and yet underestimated protein trafficking mechanism, particularly suited to regulate the localization of multifunctional proteins.
多功能蛋白通常在定位到不同的亚细胞区室时执行其不同的功能。然而，导致其定位的机制在很大程度上尚不清楚。最近，人们发现3'非翻译区（3'UTR）通过形成3'UTR-蛋白质复合物来调节新合成蛋白质的细胞定位。在此，我们通过利用大规模蛋白质-蛋白质和蛋白质-RNA相互作用网络，研究涉及多功能蛋白的3'UTR-蛋白质复合物的形成。聚焦于238种人类“极端多功能”（EMF）蛋白，我们预测了1411种涉及其中54%蛋白质的3'UTR-蛋白质复合物，并评估了它们在调节蛋白质细胞定位和多功能性方面的作用。我们发现，缺乏定位信号但同时存在于细胞核和细胞表面的EMF蛋白，通常会形成3'UTR-蛋白质复合物，并且这些复合物的形成可以为EMF蛋白提供其多功能性所需的相互作用伙伴的多样性。我们的发现通过预测会形成3'UTR-蛋白质复合物的典型兼职蛋白得到了加强。最后，涉及人类蛋白质-蛋白质相互作用网络中高达17%蛋白质的3'UTR-蛋白质复合物的形成，可能是一种常见但尚未被充分认识的蛋白质运输机制，特别适合于调节多功能蛋白的定位。
