Cyclin B Translation Depends on mTOR Activity after Fertilization in Sea Urchin Embryos

PLoS One. 2016 Mar 10;11(3):e0150318. doi: 10.1371/journal.pone.0150318. eCollection 2016.

Abstract

The cyclin B/CDK1 complex is a key regulator of mitotic entry. Using PP242, a specific ATP-competitive inhibitor of mTOR kinase, we provide evidence that the mTOR signalling pathway controls cyclin B mRNA translation following fertilization in Sphaerechinus granularis and Paracentrotus lividus. We show that PP242 inhibits the degradation of the cap-dependent translation repressor 4E-BP (eukaryotic initiation factor 4E-Binding Protein). PP242 inhibits global protein synthesis, delays cyclin B accumulation, cyclin B/CDK1 complex activation and consequently entry into the mitotic phase of the cell cycle triggered by fertilization. PP242 inhibits cyclin B mRNA recruitment into active polysomes triggered by fertilization. An amount of cyclin B mRNA present in active polysomes appears to be insensitive to PP242 treatment. Taken together, our results suggest that, following sea urchin egg fertilization, cyclin B mRNA translation is controlled by two independent mechanisms: a PP242-sensitive and an additional PP242-insentitive mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin B / biosynthesis*
  • Embryo, Nonmammalian / metabolism*
  • Fertilization / drug effects
  • Fertilization / physiology*
  • Indoles / pharmacology
  • Peptide Initiation Factors / metabolism
  • Polyribosomes / metabolism
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology*
  • Purines / pharmacology
  • RNA, Messenger / metabolism
  • Sea Urchins / metabolism
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Cyclin B
  • Indoles
  • Peptide Initiation Factors
  • Purines
  • RNA, Messenger
  • TOR Serine-Threonine Kinases
  • PP242

Grants and funding

This work was supported by research grants from “La Ligue contre le Cancer (coordination du Grand Ouest [comités Finistère, Côtes d'Armor, Deux-Sèvres, Morbihan])”, the “Région Bretagne”, and the “Conseil Général du Finistère”; by ITMO AVIESAN CNRS/INSERM for equipment grant. H. Chassé is a PhD fellow supported by the Région Bretagne.