Moreover, some peptides produced by translation of uORFs have been reported to interact with the ribosome, further diminishing the efficiency of protein translation (47,48). In contrast, regulation of yeast GCN4 translation by nutrient levels was independent of the peptide sequences encoded by its uORFs (49,50). Our current study showed that introduction of stop codon constructs (þS), thereby changing the sequence of peptide encoded by the uORF, exhibited changes similar to those seen in the translation of the downstream cistron ( Figure 5B). Furthermore, mutating the uAUGs while also introducing the stop codon (M þ S) caused a marked increase in the translation of the downstream cistron ( Figure 5D). These **data** show that regulation of the MOR uORF is independent of the peptide sequence of the uORF. Thus, the inhibitory effect of the uORF during MOR translation is a protein-independent mechanism. Although the mechanisms involved in explaining the inhibitory effects of the uORF peptide on translation are not understood, several models could be proposed. For example, the peptide of the uORF could be synthesized and have the ability to inhibit translation only at high concentrations in the local microenvironment (51).