The human translation initiation multi-factor complex promotes methionyl-tRNAi binding to the 40S ribosomal subunit

Nucleic Acids Res. 2012 Jan;40(2):905-13. doi: 10.1093/nar/gkr772. Epub 2011 Sep 22.


The delivery of Met-tRNA(i) to the 40S ribosomal subunit is thought to occur by way of a ternary complex (TC) comprising eIF2, GTP and Met-tRNA(i). We have generated from purified human proteins a stable multifactor complex (MFC) comprising eIF1, eIF2, eIF3 and eIF5, similar to the MFC reported in yeast and plants. A human MFC free of the ribosome also is detected in HeLa cells and rabbit reticulocytes, indicating that it exists in vivo. In vitro, the MFC-GTP binds Met-tRNA(i) and delivers the tRNA to the ribosome at the same rate as the TC. However, MFC-GDP shows a greatly reduced affinity to Met-tRNA(i) compared to that for eIF2-GDP, suggesting that MFC components may play a role in the release of eIF2-GDP from the ribosome following AUG recognition. Since an MFC-Met-tRNA(i) complex is detected in cell lysates, it may be responsible for Met-tRNA(i)-40S ribosome binding in vivo, possibly together with the TC. However, the MFC protein components also bind individually to 40S ribosomes, creating the possibility that Met-tRNA(i) might bind directly to such 40S-factor complexes. Thus, three distinct pathways for Met-tRNA(i) delivery to the 40S ribosomal subunit are identified, but which one predominates in vivo remains to be elucidated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Animals
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factors / metabolism*
  • HeLa Cells
  • Humans
  • Peptide Chain Initiation, Translational*
  • RNA, Transfer, Amino Acyl / metabolism*
  • Rabbits
  • Reticulocytes / metabolism
  • Ribosome Subunits, Small, Eukaryotic / metabolism*


  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factors
  • RNA, Transfer, Amino Acyl
  • tRNA(m)(Met), methionine-
  • Adenosine Diphosphate