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The C-terminal region of eukaryotic translation initiation factor 3a (eIF3a) promotes mRNA recruitment, scanning, and, together with eIF3j and the eIF3b RNA recognition motif, selection of AUG start codons.

The C-terminal domain (CTD) of the a/Tif32 subunit of budding yeast eukaryotic translation initiation factor 3 (eIF3) interacts with eIF3 subunits j/Hcr1 and b/Prt1 and can bind helices 16 to 18 of 18S rRNA, suggesting proximity to the mRNA entry channel of the 40S subunit. We have identified substitutions in the conserved Lys-Glu-Arg-Arg (KERR) motif and in residues of the nearby box6 element of the a/Tif32 CTD that impair mRNA recruitment by 43S preinitiation complexes (PICs) and confer phenotypes indicating defects in scanning and start codon recognition. The normally dispensable CTD of j/Hcr1 is required for its binding to a/Tif32 and to mitigate the growth defects of these a/Tif32 mutants, indicating physical and functional interactions between these two domains. The a/Tif32 CTD and the j/Hcr1 N-terminal domain (NTD) also interact with the RNA recognition motif (RRM) in b/Prt1, and mutations in both subunits that disrupt their interactions with the RRM increase leaky scanning of an AUG codon. These results, and our demonstration that the extreme CTD of a/Tif32 binds to Rps2 and Rps3, lead us to propose that the a/Tif32 CTD directly stabilizes 43S subunit-mRNA interaction and that the b/Prt1-RRM-j/Hcr1-a/Tif32-CTD module binds near the mRNA entry channel and regulates the transition between scanning-conducive and initiation-competent conformations of the PIC.

Pubmed ID: 20584985

Authors

  • Chiu WL
  • Wagner S
  • Herrmannová A
  • Burela L
  • Zhang F
  • Saini AK
  • Valásek L
  • Hinnebusch AG

Journal

Molecular and cellular biology

Publication Data

September 25, 2010

Associated Grants

  • Agency: Wellcome Trust, Id: 076456
  • Agency: Wellcome Trust, Id: 076456/Z/05/Z
  • Agency: FIC NIH HHS, Id: R01 TW007271
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Codon, Initiator
  • Eukaryotic Initiation Factor-3
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Peptide Initiation Factors
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • Protein Subunits
  • RNA, Messenger
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins