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

Sci Rep. 2017 Apr 27;7(1):1224. doi: 10.1038/s41598-017-01156-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Centrosome / metabolism*
  • Gene Expression Regulation*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Protein Biosynthesis*
  • Protein Interaction Mapping*
  • Proteins / metabolism*
  • RNA-Binding Proteins / metabolism*

Substances

  • Bicc1 protein, human
  • OFD1 protein, human
  • Proteins
  • RNA-Binding Proteins