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Letters to Nature

Nature 426, 579-584 (4 December 2003) | doi:10.1038/nature02160; Received 22 August 2003; Accepted 10 October 2003

Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly

Marcello Ceci1,2, Cristina Gaviraghi1,2, Chiara Gorrini1,2, Leonardo A. Sala1,2, Nina Offenhäuser3, Pier Carlo Marchisio1,2 & Stefano Biffo1,4

  1. Molecular Histology Unit, DIBIT-HSR, 20132 Milano, Italy
  2. University 'Vita-Salute' San Raffaele School of Medicine, 20132 Milano, Italy
  3. Firc Institute for Molecular Oncology, 20100 Milano, Italy
  4. Department of Science and Advanced Technology, University of Eastern Piedmont 'Amedeo Avogadro', 15100 Alessandria, Italy

Correspondence to: Stefano Biffo1,4 Email: biffo.stefano@hsr.it

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The assembly of 80S ribosomes requires joining of the 40S and 60S subunits, which is triggered by the formation of an initiation complex on the 40S subunit1. This event is rate-limiting for translation2, and depends on external stimuli3 and the status of the cell4. Here we show that 60S subunits are activated by release of eIF6 (also termed p27BBP)5, 6. In the cytoplasm, eIF6 is bound to free 60S but not to 80S. Furthermore, eIF6 interacts in the cytoplasm with RACK17, a receptor for activated protein kinase C (PKC). RACK1 is a major component of translating ribosomes, which harbour significant amounts of PKC. Loading 60S subunits with eIF6 caused a dose-dependent translational block and impairment of 80S formation, which were reversed by expression of RACK1 and stimulation of PKC in vivo and in vitro. PKC stimulation led to eIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational rescue. We propose that eIF6 release regulates subunit joining, and that RACK1 provides a physical and functional link between PKC signalling and ribosome activation.