The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets

中心体OFD1蛋白与翻译机制相互作用,并调控特定靶标的合成

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作者:Daniela Iaconis ,Maria Monti ,Mario Renda ,Arianne van Koppen ,Roberta Tammaro ,Marco Chiaravalli ,Flora Cozzolino ,Paola Pignata ,Claudia Crina ,Piero Pucci ,Alessandra Boletta ,Vincenzo Belcastro ,Rachel H Giles ,Enrico Maria Surace ,Simone Gallo ,Mario Pende ,Brunella Franco

Abstract

Protein synthesis is traditionally associated with specific cytoplasmic compartments. We now show that OFD1, a centrosomal/basal body protein, interacts with components of the Preinitiation complex of translation (PIC) and of the eukaryotic Initiation Factor (eIF)4F complex and modulates the translation of specific mRNA targets in the kidney. We demonstrate that OFD1 cooperates with the mRNA binding protein Bicc1 to functionally control the protein synthesis machinery at the centrosome where also the PIC and eIF4F components were shown to localize in mammalian cells. Interestingly, Ofd1 and Bicc1 are both involved in renal cystogenesis and selected targets were shown to accumulate in two models of inherited renal cystic disease. Our results suggest a possible role for the centrosome as a specialized station to modulate translation for specific functions of the nearby ciliary structures and may provide functional clues for the understanding of renal cystic disease.

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