Untranslated Leader Sequences and Enhanced Messenger RNA Translational Efficiency

The analysis of gene regulation has been facilitated by model experimental systems which represent the extremes of a particular mechanism; that is, by identifying examples of controls which function either with extraordinary efficiency or not at all, investigators are provided with a system which might be manipulated to characterize the underlying control elements. Messenger RNAs which translate with high-level efficiency have been studied both to define fundamental mechanisms of protein synthesis and also to gain a more complete understanding of why some messenger RNAs translate with greater efficiency than others. For some of these efficient mRNAs, experimental evidence has localized control to nucleotides at the 5′ terminus of the mRNA preceding the initiation codon--the noncoding or untranslated leader sequence. In this paper, we describe examples of high-level mRNA translational efficiency related to the noncoding 5′ leader, summarize current understanding of the mechanism of enhanced translation, and comment upon what has been learned from the study of these mRNAs.