Secondary structure of mRNA and efficiency of translation initiation.

A series of recombinant plasmids, containing the cro gene of phage lambda, exhibit strikingly different levels of expression depending apparently only on the nucleotide sequence of the untranslated 5' mRNA (Roberts et al., 1979). We postulate that initiation of translation involves interaction between an activated 30S ribosomal subunit and the 5'-terminal region of a messenger RNA already folded in a specific secondary structure. The observed variation in cro synthesis can then adequately be explained by secondary structure models which were derived for the different mRNAs. To maximize expression, it appears necessary that the initiation codon and, although less important, the ribosome interaction site are accessible.