Initiation of protein synthesis from the A site of the ribosome

Cell. 2000 Aug 18;102(4):511-20. doi: 10.1016/s0092-8674(00)00055-6.


Positioning of the translation initiation complex on mRNAs requires interaction between the anticodon of initiator Met-tRNA, associated with eIF2-GTP and 40S ribosomal subunit, and the cognate start codon of the mRNA. We show that an internal ribosome entry site located in the genome of cricket paralysis virus can form 80S ribosomes without initiator Met-tRNA, eIF2, or GTP hydrolysis, with a CCU triplet in the ribosomal P site and a GCU triplet in the A site. P-site mutagenesis revealed that the P site was not decoded, and protein sequence analysis showed that translation initiates at the triplet in the A site. Translational initiation from the A site of the ribosome suggests that the repertoire of translated open reading frames in eukaryotic mRNAs may be greater than anticipated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticodon
  • Base Sequence
  • Codon, Terminator
  • Eukaryotic Initiation Factor-2 / metabolism
  • Guanosine Triphosphate / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nucleic Acid Conformation
  • Open Reading Frames
  • Peptide Chain Initiation, Translational*
  • Protein Biosynthesis*
  • RNA, Messenger / metabolism*
  • RNA, Transfer, Met / genetics
  • Rabbits
  • Ribosomes / metabolism*


  • Anticodon
  • Codon, Terminator
  • Eukaryotic Initiation Factor-2
  • RNA, Messenger
  • RNA, Transfer, Met
  • Guanosine Triphosphate