1 SCIENTIFIC REPORTS | 7: 1224 | DOI:10.1038/s41598-017-01156-x www.nature.com/scientificreports The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets Daniela Iaconis 1 , Maria Monti 2 , Mario Renda 1 , Arianne van Koppen 3 , Roberta Tammaro 1 , Marco Chiaravalli 4 , Flora Cozzolino 2 , Paola Pignata 1 , Claudia Crina 1 , Piero Pucci 2 , Alessandra Boletta 4 , Vincenzo Belcastro 1 , Rachel H. Giles 3 , Enrico Maria Surace 1 , Simone Gallo 5 , Mario Pende 6 & Brunella Franco 1,7 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. e initiation of mRNA translation in eukaryotes is an articulated process composed of different steps. Among these, the formation of the Preinitiation complex (PIC) and of the eIF4F complex is finely regulated. Specific translation factors contribute to the modulation of initiation by interacting with the ribosome, the mRNA and/ or other translation factors. In particular, the PIC includes the 40S ribosomal subunit and several initiation fac- tors, like eIF2 and eIF3; then, eIF4E, eIF4A and eIF4G associates with the PIC to form the eIF4F complex and promote Cap-dependent translation 1–3 . Signaling pathways can impact translation at multiple steps. For instance, the phosphorylation status of eIF2α and eIF4E availability is rate limiting for translation efficiency 4, 5 . mTORC1 (mechanistic Target Of Rapamycin Complex 1) phosphorylates 4E-binding proteins (4E-BPs) and inhibits their sequestering activity towards eIF4E, thus upregulating translation 6–8 . In eukaryotic cells, a further mean of translation regulation consists in sorting mRNAs to different intracellu- lar localization. According to their destination in the cells, mRNAs can indeed be sequestered from the ribosome machinery 9 or have their translation enhanced 10 . is can be evident at both spatial and temporal levels. For instance, analysis of mRNA localization in Drosophila showed their different localization in specific cell com- partments during embryonic development 11 . Interestingly, components of the translational machinery, namely eIF4E, eIF4A1, and also 4E-BP1, have also been localized to centrosomes 12–14 . ese observations suggest a still unexplored link between the translational machinery and the centrosome. 1 Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei, 34, 80078, Pozzuoli, Naples, Italy. 2 Dipartimento di Scienze Chimiche and CEINGE Biotecnologie Avanzate, Università di Napoli Federico II, Via Gaetano Salvatore 482, 80145, Napoli, Italy. 3 Department of Nephrology and Hypertension, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands. 4 Division of Genetics and Cell Biology, Dibit, San Raffaele Scientific Institute, Via Olgettina, 58 – 20132, Milan, Italy. 5 Molecular Histology and Cell Growth Unit, INGM - Istituto Nazionale di Genetica Molecolare “Romeo and Enrica Invernizzi”, Via Francesco Sforza, 35 – 20122, Milan, Italy. 6 Institut National de la Santé et de la Recherche Médicale (INSERM) U1151, Institut Necker Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 7 Department of Translational Medicine, University of Naples “Federico II”, Via Sergio Pansini, 80131, Naples, Italy. Correspondence and requests for materials should be addressed to B.F. (email: franco@tigem.it) Received: 21 September 2016 Accepted: 8 March 2017 Published: xx xx xxxx OPEN