A role for mRNA secondary structure in the control of translation initiation.

Abstract

A role for messenger RNA (mRNA) secondary structure in the control of translation initiation has been assumed for many years1–3. Strong additional evidence supporting this notion is now provided by work on the lamB gene of Escherichia coli, which codes for a major outer membrane protein that functions both as a receptor for phages λ, K-10 and TP1, and as a component of the maltose and maltodextrin transport system4–9. Mutations that affect translation initiation of the lamB mRNA have been described previously10. DNA sequence analysis indicated that one such mutation, lamB 701, is located two nucleotides promoter-proximal to the lamB Shine–Dalgarno sequence. A second mutation, lamB 708, is located in the sixth codon of the lamB gene (see Fig. 1). Schwartz et al.10 suggested that these two point mutations affect translation initiation by favouring the formation of a base-paired hairpin structure in the lamB transcript which makes the Shine–Dalgarno sequence11 inaccessible to ribosomes (see Fig. 2). This suggestion was genetically testable because it predicted that the translation initiation defect caused by either of the two mutations alone would be suppressed in a lamB 701–708 double mutant (see Fig. 2). Here we demonstrate that the 701 and 708 mutations do indeed suppress each other, as predicted by an effect attributable to mRNA secondary structure.