Cap-Independent Translation

Whether or not an mRNA is translated is often thought to be a simple function of its steady-state concentration and the ab­ sence of inhibitory proteins or RNA structures in the 5' and 3' noncoding regions. The articles presented in this volume show an unexpected flexibility of the eukaryotic translational appara­ tus in the mechanism of translational initiation and provide new opportunities for regulation. Most or all mRNA molecules synthesized by RNA poly­ 7 merase II in eukaryotic cells contain a 5' terminal mGpppG dinucleotide, also known as the "cap structure. " RNAs carrying a cap structure have been shown to be more resistant to attack by exoribonucleases than their uncapped counterparts. Further­ more, the cap facilitates transport of the RNAs from the nucleus to the cytoplasm. In the cytoplasm, the cap functions as a binding site for the cap binding protein complex eIF-4, which enhances the translation of the RNAs by the eukaryotic trans­ lational apparatus. Specifically, it has been postulated that bind­ ing of e1F-4 to the 5' terminal cap facilitates the recruitment of ribosomal subunits onto the mRNAs via their free 5' ends (cap­ dependent translation). Accordingly, uncapped RNAs are generally translated more poorly than capped RNAs. However, during the past 6 years both viral and cellular mRNAs have been discovered that can be translated cap-independently.