Spacer-length dependence of programmed -1 or -2 ribosomal frameshifting on a U(6)A heptamer supports a role for messenger RNA (mRNA) tension in frameshifting

Lin, Zhaoru; Gilbert, Robert J. C.; Brierley, Ian

From the determined amino acid sequence, we predict that the À2 FS product is generated by tandem slippage of P-and A-site tRNAs. As the slip is À2, the P-site tRNA would re-pair on a codon that includes the base 5 0 of the U 6 A heptamer (an A in these mRNAs) and it should be noted that the post-slippage contacts following this rearrangement are suboptimal, with the codon:anticodon complex (5 0 -AUU-3 0 /5 0 -GmAA-3 0 ) mismatched at the first position. Altering the base 5 0 of the slippery sequence to GU 6 A also did not inhibit À2 FS (Supplementary Figure S1 ). However, in À1 FS, it is known that there is tolerance for mismatches at the first position of the post-slip P-site complex (12; see also Figure 4 ) and this appears to hold true for À2 FS.