We made the unexpected observation, however, that depletion of eIF4G narrows the range of translational efficiencies for a large fraction of mRNAs, decreasing the number with efficiencies that are substantially higher or lower than the genome average TE. This trend is well illustrated in the log log plots of mean TE values in WT versus mutant cells, and also by the fact that depleting eIF4G reduced the numbers of mRNAs with TE values either 1. 5 fold higher, or 1. 5 fold lower, than unity. Furthermore, the bulk of mRNAs with TE values 1. 5 in WT cells are, at least to some extent, dependent on eIF4G for their higher than average TE values. This dependence is consistent with a significant role for eIF4G in stimulat ing one or more steps of initiation for the most efficiently translated mRNAs in the cell, presumably the activation of mRNA for recruitment of the 43S PIC, scanning the 5UTR, or start codon recognition.

Unex pectedly, we found that many Inhibitors,Modulators,Libraries mRNAs with lower than average TE values in WT cells Inhibitors,Modulators,Libraries exhibit an increased translational efficiency on eIF4G depletion. It is concei vable that eIF4G directly impairs the translation of these latter mRNAs. However, we favor an indirect mechan ism involving competition among all mRNAs for limit ing initiation factors or PICs, coupled with the role of eIF4G in stimulating efficiently translated mRNAs at the expense of those with lower than average efficiencies. Batimastat In the absence of eIF4G, this competitive edge would be eliminated for the first group and thereby enable the second group of mRNAs to compete better for limiting factors PICs.

The small group of 100 genes we identified that are most dependent on eIF4G for their higher than average TEs in WT cells contain a mean 5UTR length that is slightly below the genome average for all mRNAs, a feature that should facilitate Inhibitors,Modulators,Libraries efficient scan ning and AUG recognition. This was surprising because we expected to find that the mRNAs most dependent on eIF4G would have long or highly structured 5UTRs, requiring the eIF4GeIF4A complex for unwinding sec ondary structure to promote 43S attachment or scan ning. In fact, the 100 genes we identified whose translation is stimulated the most by eliminating eIF4G contain a mean 5UTR length substantially larger than the genome average.

The fact that these latter mRNAs display a lower than average TE in WT cells and benefit from the absence of eIF4G seems to indicate that they function inefficiently Inhibitors,Modulators,Libraries at steps of initiation not significantly enhanced by eIF4G. Given their long 5 UTR lengths, it seems likely that scanning to the start codon is relatively inefficient for these mRNAs. If so, then the fact that depleting eIF4G does not exacerbate this deficiency suggests that factors besides eIF4G are more critically required for efficient scanning through long 5UTRs in yeast.