Mechanism of inhibition of eukaryotic translational initiation by the trinucleotide ApUpG.
ApUpG, the oligoribonucleotide homologous to the initiation codon, as well as the tetranucleotides ApUpGpA and ApUpGpG block initiation of protein synthesis in the rabbit reticulocyte lysate. These oligonucleotides are recognized as translational initiation sites by the ribosomes, leading to a very large accumulation of complete, but inactive, 80 S initiation complexes, containing methionylated initiator tRNA and ApUpG in a 1:1 stoichiometry. ApUpG appears to inhibit by competing with endogenous globin mRNA for 80 S ribosomal couples, since the inhibition of protein synthesis by ApUpG can be largely relieved by increasing the globin mRNA. The 80 S.Met-tRNAiMet.ApUpG complexes are not formed in the absence of hemin, demonstrating that their formation requires the active recycling of eukaryotic initiation factor 2. In addition the trinucleotide correctly directs the Met-tRNAiMet into the ribosomal donor site, since the methionyl residue is puromycin-reactive.
Wagner
T
T
Department of Biochemistry, University of Chicago, IL 60637.
Sigler
P B
PB
Gross
M
M
D000818:Animals; D001665:Binding Sites; D003062:Codon; D009843:Oligoribonucleotides / Q000494:pharmacology*; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects*; D011691:Puromycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects*; D012345:RNA, Transfer, Amino Acid-Specific / Q000378:metabolism*; D012358:RNA, Transfer, Met / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism*
D003062:Codon; D009843:Oligoribonucleotides; D012333:RNA, Messenger; D012345:RNA, Transfer, Amino Acid-Specific; D012358:RNA, Transfer, Met; C017020:ApUpG; D011691:Puromycin