Parameters Determining Translational Efficiency of an mRNA Species

PARAMETERS DETERMINING TRANSLATIONAL EFFICIENCY OF AN mRNA SPECIES 

One of the outstanding questions that remains to be clarified is the very wide range in initiation efficiency encountered among eu- 

The role of the 5 -leader sequence in determining initiation efficiency is difficult to determine on the basis of presently available data. This point is well illustrated by the five mRNA species of VSV. In vivo, these mRNAs are apparently translated with identical efficiencies of initiation (Villareal et ai, 1976), yet they possess 5 leaders that are unrelated in sequence and vary in length from 10-41 nucleotides (Rose, 1980). 

This variation in 5 ends in the face of identical initiation efficiency suggests that it may not be the leader sequence per se that determines initiation strength, but the interaction of this sequence with other, internal parts of the mRNA molecule. Since the coding sequence in an mRNA molecule is dictated by the individual protein encoded, and since the 3 -untranslated sequence is also highly variable (Section 3.5), any stable interaction between 5 leader and internal sequences is only possible if the leader sequence is especially tailored to allow such a fit. If this view is correct, then an important determinant for the efficiency of initiation is the structure generated by this interaction around the initiation codon. 

The fact that denaturation of eukaryotic mRNA does not lead to binding of ribosomes at internal sites in mRNA (Kozak, 1980a Collins et ai, 1982 Zagorska et ai, 1982) is not in conflict with this concept. It merely indicates that structure in mRNA is not important for determining where initiation occurs. As mentioned in Section 3.1, this point should be separated clearly from the question of how often initiation takes place. Two mRNA species can vary widely in initiation efficiency even if, as is generally the case, initiation occurs at the first AUG codon in both. It is here that the contribution of structure may be of essence. 

---