Altered discrimination of start codons and initiator tRNAs by mutant initiation factor 3. 2001

M O'Connor, and S T Gregory, and U L Rajbhandary, and A E Dahlberg
Department of Molecular and Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA. Michael_O'Connor@Brown.edu

IF3 is essential for ensuring the fidelity of the initiation step of translation in bacterial cells. Mutations at residues R99 and R131 in the C-terminal domain of the factor have previously been shown to increase initiation from the non-canonical GUA codon. Here we show that these mutant forms of IF3 fail to discriminate against initiation from many different non-AUG codons. They also enhance the activity of mutant tRNAs carrying changes in the three consecutive G-C pairs that are conserved in the anticodon stem of initiator tRNAs. In addition, the IF3 mutants stimulate initiations from leaderless mRNAs and from internal initiation codons, in the absence of any SD-anti-SD interaction. These results indicate that IF3 ensures the accuracy of initiation by inspecting both the codon-anticodon pairing and unique features of the initiator tRNA as well as suppressing initiation from other potential start sites within the mRNA.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D010448 Peptide Initiation Factors Protein factors uniquely required during the initiation phase of protein synthesis in GENETIC TRANSLATION. Initiation Factors,Initiation Factor,Factors, Peptide Initiation,Initiation Factors, Peptide
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D012343 RNA, Transfer The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains. Suppressor Transfer RNA,Transfer RNA,tRNA,RNA, Transfer, Suppressor,Transfer RNA, Suppressor,RNA, Suppressor Transfer
D018387 Codon, Initiator A codon that directs initiation of protein translation (TRANSLATION, GENETIC) by stimulating the binding of initiator tRNA (RNA, TRANSFER, MET). In prokaryotes, the codons AUG or GUG can act as initiators while in eukaryotes, AUG is the only initiator codon. Codon, Start,Initiator Codon,Codon, Initiation,Start Codon,Codons, Initiation,Codons, Initiator,Codons, Start,Initiation Codon,Initiation Codons,Initiator Codons,Start Codons
D039621 Eukaryotic Initiation Factor-3 A multisubunit eukaryotic initiation factor that contains at least 8 distinct polypeptides. It plays a role in recycling of ribosomal subunits to the site of transcription initiation by promoting the dissociation of non-translating ribosomal subunits. It also is involved in promoting the binding of a ternary complex of EUKARYOTIC INITIATION FACTOR-2; GTP; and INITIATOR TRNA to the 40S ribosomal subunit. EIF-3,Peptide Initiation Factor EIF-3,EIF3,EIF3 p110,EIF3 p42 Protein,EIF3-alpha,EIF3-beta,EIF3-epsilon,EIF3-gamma,EIF3-p48,EIF3-zeta,EIF3S3 Gene Product,EIF3S3 Protein,EIF3S4 Protein,Eukaryotic Initiation Factor-3 p110,Eukaryotic Initiation Factor-3, Subunit 1,Eukaryotic Initiation Factor-3, Subunit 2,Eukaryotic Initiation Factor-3, Subunit 3,Eukaryotic Initiation Factor-3, Subunit 4,Eukaryotic Initiation Factor-3, Subunit 5,Eukaryotic Initiation Factor-3, Subunit 6,Eukaryotic Initiation Factor-3, Subunit 7,Eukaryotic Initiation Factor-3, Subunit 8,Eukaryotic Initiation Factor-3, beta Subunit,Eukaryotic Initiation Factor-3, delta Subunit,Eukaryotic Initiation Factor-3, gamma Subunit,Eukaryotic Initiation Factor-3, zeta Subunit,Eukaryotic Peptide Initiation Factor 3, Subunit 5,Eukaryotic Peptide Initiation Factor-3,Eukaryotic Peptide Initiation Factor-3, Subunit 1,Eukaryotic Peptide Initiation Factor-3, Subunit 2,Eukaryotic Peptide Initiation Factor-3, Subunit 3,Eukaryotic Peptide Initiation Factor-3, Subunit 4,Eukaryotic Peptide Initiation Factor-3, alpha Subunit,Eukaryotic Translation Initiation Factor-3, Subunit 8,INT6 Protein,Int-6 Gene Product,Int-6 Protein,p42 EIF3 Protein,EIF3 Protein, p42,EIF3 alpha,EIF3 epsilon,EIF3 gamma,Eukaryotic Initiation Factor 3,Eukaryotic Initiation Factor 3 p110,Eukaryotic Initiation Factor 3, Subunit 1,Eukaryotic Initiation Factor 3, Subunit 2,Eukaryotic Initiation Factor 3, Subunit 3,Eukaryotic Initiation Factor 3, Subunit 4,Eukaryotic Initiation Factor 3, Subunit 5,Eukaryotic Initiation Factor 3, Subunit 6,Eukaryotic Initiation Factor 3, Subunit 7,Eukaryotic Initiation Factor 3, Subunit 8,Eukaryotic Initiation Factor 3, beta Subunit,Eukaryotic Initiation Factor 3, delta Subunit,Eukaryotic Initiation Factor 3, gamma Subunit,Eukaryotic Initiation Factor 3, zeta Subunit,Eukaryotic Peptide Initiation Factor 3,Eukaryotic Peptide Initiation Factor 3, Subunit 1,Eukaryotic Peptide Initiation Factor 3, Subunit 2,Eukaryotic Peptide Initiation Factor 3, Subunit 3,Eukaryotic Peptide Initiation Factor 3, Subunit 4,Eukaryotic Peptide Initiation Factor 3, alpha Subunit,Eukaryotic Translation Initiation Factor 3, Subunit 8,Gene Product, Int-6,Initiation Factor-3, Eukaryotic,Int 6 Gene Product,Int 6 Protein,Peptide Initiation Factor EIF 3

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