Maintenance of protein synthesis reading frame by EF-P and m1G37-tRNA

Maintaining the translational reading frame poses difficulty for the ribosome. Slippery mRNA sequences such as CC[C/U]-[C/U], read by isoacceptors of tRNAPro, are highly prone to +1 frameshift (+1FS) errors. Here we show that +1FS errors occur by two mechanisms, a slow mechanism when tRNAPro is stalled in the P-site next to an empty A-site and a fast mechanism during translocation of tRNAPro into the P-site. Suppression of +1FS errors requires the m1G37 methylation of tRNAPro on the 3' side of the anticodon and the translation factor EF-P. Importantly, both m1G37 and EF-P show the strongest suppression effect when CC[C/U]-[C/U] are placed at the second codon of a reading frame. This work demonstrates that maintaining the reading frame immediately after the initiation of translation by the ribosome is an essential aspect of protein synthesis. Slippery mRNA sequences CC[C/U]-[C/U] are prone to +1 frameshift (+1FS) errors during mRNA translation. Here, the authors show that +1FS errors occur predominantly when CC[C/U]-[C/U] are placed at the second sense codon, and that error suppression requires m1G37-tRNA and the translation factor EF-P.