Maintenance of protein synthesis reading frame by EF-P and m 1 G37-tRNA

Howard B. Gamper; Isao Masuda; Milana Frenkel-Morgenstern; Ya Ming Hou

doi:10.1038/ncomms8226

Maintenance of protein synthesis reading frame by EF-P and m 1 G37-tRNA

Howard B. Gamper, Isao Masuda, Milana Frenkel-Morgenstern, Ya Ming Hou

Bar-Ilan University - Azrieli Faculty of Medicine

Thomas Jefferson University

Research output: Contribution to journal › Article › peer-review

74 Scopus citations

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 tRNA^Pro, are highly prone to +1 frameshift (+FS) 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 tRNA^Pro into the P-site. Suppression of +FS errors requires the m¹G37 methylation of tRNA^Pro 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.

Original language	English
Article number	7226
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8226
State	Published - 26 May 2015

Bibliographical note

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

Funding

We thank Takao Igarashi for construction of overexpression tRNA clones, Barry Cooperman for reagents of E. coli ribosomes and purified factors, Takuya Ueda for release factor constructs, Hani Zaher and Rachel Green for instructions on electrophoretic TLC analysis and release factor assay, James Curran for the lacZ construct, Myung Hee Park for EF-P expression clones, Glenn Björk for S. typhimurium strains, and Allen Buskirk, Ruben Gonzalez and Claudio Gualerzi for discussion. We apologize to colleagues whose studies were not cited due to space limitations. This work was supported by NIH grant GM081601 to Y.-M.H.

Funders	Funder number
National Institutes of Health	GM081601
National Institute of General Medical Sciences	U01GM108972

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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 (+FS) 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 +FS 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.",

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Maintenance of protein synthesis reading frame by EF-P and m 1 G37-tRNA

Abstract

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Funding

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