HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome

Mouzakis, Kathryn D.; Lang, Andrew L.; Vander Meulen, Kirk A.; Easterday, Preston D.; Butcher, Samuel E.

Frameshift efficiencies for the different RNA constructs were measured (Figure 3 and Table 1 ). Increases in the local stability of the first 3 bp resulted in significant increases in frameshift efficiency ( Figure 3A, MS1-5 ). In contrast, sequence changes that significantly lowered the local stability of the first 3 bp resulted in decreased frameshift efficiencies ( Figure 3A , MS10-12 and Table 1 ). No correlation between frameshift efficiency and overall thermodynamic stability is observed ( Figure 3B ). Instead, we observe a strong correlation (R 2 = 0.88) between frameshift efficiency and local stability of the first 3 bp at the base of the stem-loop using a one-phase exponential decay function ( Figure 3C and Supplementary Table S3 ). The frameshift efficiency for each variant frameshift site can be predicted using the parameters derived from the correlation, and each predicted frameshift efficiency falls within 1 SD of its measured value (data not shown). These results support the hypothesis that the stability of the base pairs at the base of the stem-loop is a primary determinant of frameshift efficiency.