At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells.
Sequences flanking the AUG initiator codon influence its recognition by eukaryotic ribosomes. From a comparison of several hundred mRNA sequences, CCA/GCCAUGG emerged as the consensus sequence for initiation in higher eukaryotes. Systematic mutagenesis of a cloned preproinsulin gene confirmed the facilitating effect of A or G in position -3 (i.e. 3 nucleotides upstream from the AUG codon), C in positions -1 and -2, and G immediately following the AUG codon. The analysis of a new set of mutants now reveals that sequences slightly farther upstream are also influential, the optimal context for initiation being (GCC)GCCA/GCCAUGG. Possible mechanistic implications of the repeating GCC motif are discussed.
Kozak
M
M
Department of Biological Sciences, University of Pittsburgh, PA 15260.
D001483:Base Sequence; D003062:Codon; D007328:Insulin; D009154:Mutation; D011384:Proinsulin / Q000235:genetics; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger
D003062:Codon; D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; C013737:preproinsulin; D011384:Proinsulin