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ACG, the initiator codon for a Sendai virus protein.

1988; Elsevier BV; Volume: 263; Issue: 18 Linguagem: Inglês

10.1016/s0021-9258(18)68338-3

1083-351X

K.C. Gupta, Sandeep Patwardhan,

Virology and Viral Diseases

Deletion andsite-directed point mutants of the polycistronic P/C mRNA of Sendai virus revealed that one of the nonstructural proteins of this virus, the C' protein, initiates from an ACG codon.This ACG codon occurs in an optimum sequence context and precedes the first AUG of the P/C mRNA.The results presented in this communication are consistent with the concept that the ribosomes scan the P/C mRNA to initiate several proteins from its different initiator codons.The arrangement of several weak initiator codons in tandem in an mRNA, Le. non-AUG in optimum sequence context and AUG in suboptimum sequence context, may represent an alternate means to regulate gene expression in eukaryotes and their viruses.Several non-AUG initiator codons are recognized by prokaryotic ribosomes (Gold et al., 1981;Kozak, 1983).In contrast, no distinct examples for the utilization of non-AUG initiator codons in eukaryotes have been identified (Kozak, 1983).Yeast ribosomes have been shown to recognize UUG and AUA triplets as the initiator codons in mRNAs from artificial gene constructs (Zitomer et al., 1984).A proposition for the possible utilization of an ACG initiator codon in higher eukaryotes was advanced on the basis of the nucleic acid sequence and protein products of adeno-associated virus (Becerra et al., 1985).Bacteriophage T7 gene 0.3 in which the original AUG codon was substituted with ACG codon was observed to initiate protein synthesis in a wheat germ lysate translation system (Anderson and Buzash-Pollert, 1985).Similarly, based on cell-free translation and in vivo expression of mouse dihydrofolate reductase mRNA with AUG replaced with ACG, Peabody (1987) suggested that an ACG triplet may be recognized as an initiator codon in higher eukaryotes.In this communication, we show that an ACG triplet of a viral mRNA is recognized as an initiator codon by the eukaryotic ribosomes for the synthesis of a virus-specific protein.We have been trying to understand initiation of translation of three proteins from a single viral mRNA species (Gupta and Kingsbury, 1985;Gupta, 1987).The mRNA is encoded by the P/C gene of Sendai virus, a cytoplasmic negativestrand RNA virus.The P/C mRNA in Sendai virus-infected cells (Lamb and Choppin, 1978) and in cell-free translation systems (Etkind et al., 1980) is translated into three proteins,