On the origin of the cap-dependent initiation of translation in eukaryotes

The Shine-Dalgarno sequence of prokaryotic mRNAs, which helps to bind and position the ribosome at the start site for protein synthesis, is absent from eukaryotic mRNAs. Instead, for most, a structure at the 5′ end and a much larger number of protein initiation factors are needed for both binding of the ribosome and for successful start-site selection, that is, a ‘cap-dependent’ initiation mechanism. Although the mechanics of this process are well studied, what is not clear is how it evolved. By analyzing recent progress in different fields, I suggest that it was the need to adjust to the arrival of the nuclear membrane and the subsequent requirement to export intron-less mRNAs to the cytoplasm that spurred the shift to the more complex translation initiation mechanism in eukaryotes.