title: Maintenance of protein synthesis reading frame by EF-P and m(1)G37-tRNA.
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 (+1FS) errors. Here we show that +1FS errors occur by two mechanisms, a slow mechanism when tRNA(Pro) 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 +1FS errors requires the m(1)G37 methylation of tRNA(Pro) on the 3' side of the anticodon and the translation factor EF-P. Importantly, both m(1)G37 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Howard B
authors.initials: HB
authors.lastname: Gamper
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Isao
authors.initials: I
authors.lastname: Masuda
authors.affiliation: Faculty of Medicine, Bar-Ilan University, Henrietta Szold 8, Safed 1311502, Israel.
authors.forename: Milana
authors.initials: M
authors.lastname: Frenkel-Morgenstern
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Ya-Ming
authors.initials: YM
authors.lastname: Hou
mesh_terms: D004926:Escherichia coli; D016368:Frameshift Mutation; D010445:Peptide Elongation Factors / Q000378:metabolism; D014176:Protein Biosynthesis; D016364:Reading Frames; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D010445:Peptide Elongation Factors; C020746:factor EF-P