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Int J Mol Sci
2019 Feb 01;203:. doi: 10.3390/ijms20030626.
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Translational Control of Canonical and Non-Canonical Translation Initiation Factors at the Sea Urchin Egg to Embryo Transition.
Chassé H
,
Boulben S
,
Cormier P
,
Morales J
.
Abstract
Sea urchin early development is a powerful model to study translational regulation under physiological conditions. Fertilization triggers an activation of the translation machinery responsible for the increase of protein synthesis necessary for the completion of the first embryonic cell cycles. The cap-binding protein eIF4E, the helicase eIF4A and the large scaffolding protein eIF4G are assembled upon fertilization to form an initiation complex on mRNAs involved in cap-dependent translation initiation. The presence of these proteins in unfertilized and fertilized eggs has already been demonstrated, however data concerning the translational status of translation factors are still scarce. Using polysome fractionation, we analyzed the impact of fertilization on the recruitment of mRNAs encoding initiation factors. Strikingly, whereas the mRNAs coding eIF4E, eIF4A, and eIF4G were not recruited into polysomes at 1 h post-fertilization, mRNAs for eIF4B and for non-canonical initiation factors such as DAP5, eIF4E2, eIF4E3, or hnRNP Q, are recruited and are differentially sensitive to the activation state of the mechanistic target of rapamycin (mTOR) pathway. We discuss our results suggesting alternative translation initiation in the context of the early development of sea urchins.
Figure 1. (A) Optical density profiles (ODA254) of polysome fractionation from unfertilized eggs (UnF), embryos at 1 h post-fertilization (F) and in presence of puromycin (F+puro). Fractions 1 and 21 correspond to top and bottom, respectively, of the 15–40% sucrose gradient; (B) Distribution in polysomes of mRNAs encoding initiation factors eIF4G, eIF4A, eIF4B, and poly(A)-binding protein (PABP) before fertilization (UnF, square), at 1 h post-fertilization (F, black dot), and at 1 h post-fertilization in presence of puromycin (F+puro in vivo, white dot). mRNAs were detected by RT-PCR of RNA purified from each fraction of the gradient. Amplified products were separated on agarose gel and quantified as described in the Materials and Methods section. Distribution is shown as a percentage of total mRNA (n = 5; UnF vs. F: * p-value < 0.05, ** p-value < 0.01).
Figure 2. Distribution of mRNAs for eIF4E2, eIF4E3, hnRNP Q and DAP5 in polysomes, monitored as in Figure 1 (n = 5; UnF vs. F: * p-value < 0.05, ** p-value < 0.01).
Figure 4. (A) mTOR inhibition and dual mTOR/MAPK inhibition impacts protein synthesis activity. Protein synthesis activity is measured by incorporation of [35S]-methionine in TCA-precipitated proteins, normalized to the values in fertilized control embryos (representative of two independent experiments). (B) Polysome profile of fertilized embryos (F) with or without PP242 and U0126 inhibitors. (C) Redistribution of mRNAs for eIF4B (top) and DAP5 (bottom) on polysome gradients, monitored as in Figure 1, in presence of U0126 (left) or in combination with PP242 (right). Values are shown as a mean of three biological replicates, error bars represent SEM (F+PP242 vs. F+PP242+U0126: * p-value < 0.05; F+PP242 +U0126 vs. F+PP242+puro: † p-value < 0.05).
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