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

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  • Howard B. Gamper

    (Thomas Jefferson University)

  • Isao Masuda

    (Thomas Jefferson University)

  • Milana Frenkel-Morgenstern

    (Faculty of Medicine, Bar-Ilan University)

  • Ya-Ming Hou

    (Thomas Jefferson University)

Abstract

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.

Suggested Citation

  • Howard B. Gamper & Isao Masuda & Milana Frenkel-Morgenstern & Ya-Ming Hou, 2015. "Maintenance of protein synthesis reading frame by EF-P and m1G37-tRNA," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8226
    DOI: 10.1038/ncomms8226
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