This study demonstrates that eukaryotic initiation factors-4E and -4F are required for both 5' cap-dependent and internal initiation of protein synthesis, challenging the previous model that internal initiation is independent of these factors.
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Challenges prior models of internal initiation; leaves open relevance to cardiac protein synthesis in vivo.
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.
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Scheper et al. (1992) studied this question.
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