Figure 7

A stoichiometric model for eIF4E binding highlights the CAF20 and EAP1 mRNAs as significant outliers. (A) Diagram showing the theoretical basis for the stoichiometric model where the four proteins, eIF4G1, eIF4G2, Caf20p and Eap1p, all bind the cap binding protein eIF4E, which in turn binds mRNAs in a complex equilibria. This model presumes the eIF4E mRNA binding profile can be modeled via a linear combination of the other closed loop protein profiles. (B) Heatmaps of mRNA enrichment for each of the four eIF4E binding proteins, and a predicted mRNA enrichment heatmap for eIF4E based on a best fit of the model to the RIP-seq data, which in turn can be compared with the observed mRNA enrichment for eIF4E. An excellent correlation is observed between the predicted and observed heat map profiles, with R² = 0.75. (C) Equation detailing the assertion that the binding profile for eIF4E is equal to the sum of the profiles observed for all of the eIF4E binding proteins, with the corresponding β coefficients representing the contribution of each individual profile to the overall model (all significant P < 0.002). (D) A plot showing the fitted model values and the corresponding residuals from the linear regression modeling. Notably, the CAF20 and EAP1 mRNAs are significant outliers from the model when plotting their residuals from the predicted eIF4E enrichment values.