1. The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets
- Author
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Claudia Crina, Maria Chiara Monti, Simone Gallo, Roberta Tammaro, Brunella Franco, Marco Chiaravalli, Flora Cozzolino, Paola Pignata, Enrico Maria Surace, Daniela Iaconis, Vincenzo Belcastro, Alessandra Boletta, Piero Pucci, Rachel H. Giles, Mario Renda, Mario Pende, Arianne van Koppen, Iaconis, Daniela, Monti, Maria, Renda, M., van Koppen, A., Tammaro, R., Chiaravalli, M., Cozzolino, Flora, Pignata, P., Crina, C., Pucci, Pietro, Boletta, A., Belcastro, V., Giles, R. H., Surace, Enrico Maria, Gallo, S., Pende, M., and Franco, Brunella
- Subjects
0301 basic medicine ,Translation ,Science ,Biology ,Article ,03 medical and health sciences ,Polycystic kidney disease ,Eukaryotic initiation factor ,Protein Interaction Mapping ,Protein biosynthesis ,Journal Article ,Humans ,Basal body ,Centrosome ,Messenger RNA ,Multidisciplinary ,Proteins ,RNA-Binding Proteins ,Translation (biology) ,Cell biology ,HEK293 Cells ,030104 developmental biology ,Gene Expression Regulation ,Cytoplasm ,Protein Biosynthesis ,Transcription preinitiation complex ,Medicine ,HeLa Cells - 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.
- Published
- 2017