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

D Iaconis, M Monti, M Renda, A Van Koppen, R Tammaro, Marco Chiaravalli, Flora Cozzolino, P Pignata, C Crina, Piero Pucci, A Boletta, V Belcastro, RH Giles, EM Surace, S Gallo, M Pende, B Franco

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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. © 2017 The Author(s).
Original languageEnglish
Article number1224
JournalScientific Reports
Volume7
Issue number11
DOIs
Publication statusPublished - 2017

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Cystic Kidney Diseases
Centrosome
Eukaryotic Initiation Factor-4F
Basal Bodies
Kidney
Proteins
Protein Biosynthesis
Carrier Proteins
Messenger RNA

Cite this

Iaconis, D., Monti, M., Renda, M., Van Koppen, A., Tammaro, R., Chiaravalli, M., ... Franco, B. (2017). The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets. Scientific Reports, 7(11), [1224]. https://doi.org/10.1038/s41598-017-01156-x

The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets. / Iaconis, D; Monti, M; Renda, M; Van Koppen, A; Tammaro, R; Chiaravalli, Marco; Cozzolino, Flora; Pignata, P; Crina, C; Pucci, Piero; Boletta, A; Belcastro, V; Giles, RH; Surace, EM; Gallo, S; Pende, M; Franco, B.

In: Scientific Reports, Vol. 7, No. 11, 1224, 2017.

Research output: Contribution to journalArticle

Iaconis, D, Monti, M, Renda, M, Van Koppen, A, Tammaro, R, Chiaravalli, M, Cozzolino, F, Pignata, P, Crina, C, Pucci, P, Boletta, A, Belcastro, V, Giles, RH, Surace, EM, Gallo, S, Pende, M & Franco, B 2017, 'The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets', Scientific Reports, vol. 7, no. 11, 1224. https://doi.org/10.1038/s41598-017-01156-x
Iaconis, D ; Monti, M ; Renda, M ; Van Koppen, A ; Tammaro, R ; Chiaravalli, Marco ; Cozzolino, Flora ; Pignata, P ; Crina, C ; Pucci, Piero ; Boletta, A ; Belcastro, V ; Giles, RH ; Surace, EM ; Gallo, S ; Pende, M ; Franco, B. / The centrosomal OFD1 protein interacts with the translation machinery and regulates the synthesis of specific targets. In: Scientific Reports. 2017 ; Vol. 7, No. 11.
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AB - 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. © 2017 The Author(s).

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