The scanning mechanism of eukaryotic translation initiation.
In eukaryotes, the translation initiation codon is generally identified by the scanning mechanism, wherein every triplet in the messenger RNA leader is inspected for complementarity to the anticodon of methionyl initiator transfer RNA (Met-tRNAi). Binding of Met-tRNAi to the small (40S) ribosomal subunit, in a ternary complex (TC) with eIF2-GTP, is stimulated by eukaryotic initiation factor 1 (eIF1), eIF1A, eIF3, and eIF5, and the resulting preinitiation complex (PIC) joins the 5' end of mRNA preactivated by eIF4F and poly(A)-binding protein. RNA helicases remove secondary structures that impede ribosome attachment and subsequent scanning. Hydrolysis of eIF2-bound GTP is stimulated by eIF5 in the scanning PIC, but completion of the reaction is impeded at non-AUG triplets. Although eIF1 and eIF1A promote scanning, eIF1 and possibly the C-terminal tail of eIF1A must be displaced from the P decoding site to permit base-pairing between Met-tRNAi and the AUG codon, as well as to allow subsequent phosphate release from eIF2-GDP. A second GTPase, eIF5B, catalyzes the joining of the 60S subunit to produce an 80S initiation complex that is competent for elongation.
Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; email: ahinnebusch@nih.gov.
Alan G
AG
Hinnebusch
D000818:Animals; D020029:Base Pairing; D001665:Binding Sites; D018387:Codon, Initiator; D015977:Eukaryotic Initiation Factor-1 / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D040061:Eukaryotic Initiation Factor-5 / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D008715:Methionine / Q000737:chemistry; D011485:Protein Binding; D020365:RNA Helicases / Q000737:chemistry; D012358:RNA, Transfer, Met / Q000235:genetics*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry; D013768:Tetrahymena
D018387:Codon, Initiator; D015977:Eukaryotic Initiation Factor-1; D039621:Eukaryotic Initiation Factor-3; D040061:Eukaryotic Initiation Factor-5; D012358:RNA, Transfer, Met; D006160:Guanosine Triphosphate; D008715:Methionine; D020365:RNA Helicases
eIFs; initiation; ribosome; scanning; tRNA; translation