title: Shine-Dalgarno interaction prevents incorporation of noncognate amino acids at the codon following the AUG.
abstract: During translation, usually only one in approximately 400 misincorporations affects the function of a nascent protein, because only chemically similar near-cognate amino acids are misincorporated in place of the cognate one. The deleterious misincorporation of a chemically dissimilar noncognate amino acid during the selection process is precluded by the presence of a tRNA at the ribosomal E-site. However, the selection of first aminoacyl-tRNA, directly after initiation, occurs without an occupied E-site, i.e., when only the P-site is filled with the initiator tRNA and thus should be highly error-prone. Here, we show how bacterial ribosomes have solved this accuracy problem: In the absence of a Shine-Dalgarno (SD) sequence, the first decoding step at the A-site after initiation is extremely error-prone, even resulting in the significant incorporation of noncognate amino acids. In contrast, when a SD sequence is present, the incorporation of noncognate amino acids is not observed. This is precisely the effect that the presence of a cognate tRNA at the E-site has during the elongation phase. These findings suggest that during the initiation phase, the SD interaction functionally compensates for the lack of codon-anticodon interaction at the E-site by reducing the misincorporation of near-cognate amino acids and prevents noncognate misincorporation.
authors.affiliation: Max-Planck-Institut für Molekulare Genetik, AG Ribosomen, Ihnestrasse 73, D-14195 Berlin, Germany.
authors.forename: Viviana
authors.initials: V
authors.lastname: Di Giacco
authors.forename: Viter
authors.initials: V
authors.lastname: Márquez
authors.forename: Yan
authors.initials: Y
authors.lastname: Qin
authors.forename: Markus
authors.initials: M
authors.lastname: Pech
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Triana-Alonso
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Wilson
authors.forename: Knud H
authors.initials: KH
authors.lastname: Nierhaus
mesh_terms: D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D003062:Codon / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D003062:Codon; D012333:RNA, Messenger; D012346:RNA, Transfer, Amino Acyl