Internal initiation of translation directed by the 5'-untranslated region of the mRNA for eIF4G, a factor involved in the picornavirus-induced switch from cap-dependent to internal initiation.
The eIF4 group initiation factors carry out recognition of the mRNA cap, unwinding of mRNA secondary structure, and binding of mRNA to the 43 S preinitiation complex. Infection by picornaviruses results in proteolytic cleavage of one of these factors, eIF4G, an event that severely restricts cap-dependent translation but permits cap-independent initiation to proceed from internal ribosome entry sequences in picornaviral RNAs. The 5'-untranslated region (5'-UTR) of eIF4G mRNA resembles such picornaviral sequences in being unusually long and containing multiple open reading frames and a polypyrimidine tract. When inserted upstream of a luciferase reporter gene, this 5'-UTR served as a translational enhancer in four different cell lines. Mutation of all four upstream ATG codons to AAG did not alter the translational enhancement. The presence of the eIF4G 5'-UTR between an RNA hairpin and the luciferase cistron stimulated expression 119-fold. Similarly, the presence of the 5'-UTR between the two cistrons of a bicistronic mRNA stimulated expression of the downstream cistron 42-fold. These results indicate that the eIF4G 5'-UTR directs internal initiation. The ability to continue synthesis of eIF4G when the cell is unable to carry out normal cap-dependent translation may represent an autoregulatory mechanism or be part of the cellular response to stresses that interrupt cap-dependent translation.
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Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Rhoads
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D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010849:Picornaviridae / Q000378:metabolism*; D010957:Plasmids; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D010448:Peptide Initiation Factors; D012333:RNA, Messenger