Eukaryotic initiation factors-4E and -4F stimulate 5' cap-dependent as well as internal initiation of protein synthesis.
Two mechanisms of initiation of protein synthesis are known. The 5' cap-dependent model requires the activity of cap-binding eukaryotic initiation factors (eIF)1-4E and -4F, inducing unwinding of mRNA secondary structures. The internal initiation model is 5' cap-independent and requires a ribosomal entry site formed by higher order structures of the mRNA. It has been proposed that this mechanism does not need eIF-4E and eIF-4F. We prepared bicistronic transcripts on which both mechanisms of initiation occur, allowing the determination of the initiation factor dependence of these two mechanisms simultaneously. The unwinding factors eIF-4A, eIF-4B, and eIF-4F were found to be necessary for 5' cap-dependent initiation as well as for internal initiation. Surprisingly, efficient translation of both cistrons on the bicistronic mRNA required eIF-4E. A model is presented in which assembly of eIF-4E into a functional eIF-4F complex is a prerequisite for both types of initiation.
Scheper
G C
GC
Department of Molecular Cell Biology, The Netherlands.
Voorma
H O
HO
Thomas
A A
AA
D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D005814:Genes, Viral; D008969:Molecular Sequence Data; D009029:Mosaic Viruses / Q000235:genetics; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010957:Plasmids; D012315:RNA Caps; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D039561:Eukaryotic Initiation Factor-4E; D039562:Eukaryotic Initiation Factor-4F; D010448:Peptide Initiation Factors; D012315:RNA Caps; D012333:RNA, Messenger