Deforges Jules, Locker Nicolas, Sargueil Bruno
CNRS UMR8015, laboratoire de cristallographie et RMN biologiques, France; Université Paris Descartes, 4 avenue de l'observatoire, Paris Cedex 06, 75270, France.
University of Surrey, Faculty of Health and Medical Sciences, School of Biosciences and Medicine, Guildford, United Kingdom.
Biochimie. 2015 Jul;114:48-57. doi: 10.1016/j.biochi.2014.12.008. Epub 2014 Dec 18.
The accuracy of start codon selection is determined by the translation initiation process. In prokaryotes the initiation step on most mRNAs relies on recruitment of the small ribosomal subunit onto the initiation codon by base pairing between the mRNA and the 16S rRNA. Eukaryotes have evolved a complex molecular machinery involving at least 11 initiation factors, and mRNAs do not directly recruit the small ribosomal subunit. Instead the initiation complex is recruited to the 5' end of the mRNA through a complex protein network including eIF4E that interacts with the 5' cap structure and poly-A binding protein that interacts with the 3'end. However, some viral and cellular mRNAs are able to escape this pathway by internal recruitment of one or several components of the translation machinery. Here we review those eukaryotic mRNAs that have been reported to directly recruit the 40S ribosomal subunit internally. In the well characterized cases of viral IRESes, a specific RNA structure is involved in this process, and in addition to recruitment of the ribosome, the mRNA also manipulates the ribosome structure to stimulate the first translocation step. We also review recently described IRES/ribosome interactions in cases where the molecular mechanism leading to translation initiation has yet to be described. Finally we evaluate the possibility that mRNA may recruit the 40S ribosomal subunit through base pairing with the 18S rRNA.
起始密码子选择的准确性由翻译起始过程决定。在原核生物中，大多数mRNA的起始步骤依赖于mRNA与16S rRNA之间的碱基配对，将小核糖体亚基招募到起始密码子上。真核生物进化出了一种复杂的分子机制，涉及至少11种起始因子，且mRNA不会直接招募小核糖体亚基。相反，起始复合物通过一个复杂的蛋白质网络被招募到mRNA的5'端，该网络包括与5'帽结构相互作用的eIF4E和与3'端相互作用的多聚腺苷酸结合蛋白。然而，一些病毒和细胞mRNA能够通过内部招募翻译机制的一个或几个组分来避开这条途径。在这里，我们综述那些已报道的能在内部直接招募40S核糖体亚基的真核生物mRNA。在病毒内部核糖体进入位点（IRES）的典型案例中，一个特定的RNA结构参与了这一过程，并且除了招募核糖体之外，mRNA还操纵核糖体结构以刺激第一步转位。我们还综述了最近描述的IRES/核糖体相互作用，这些案例中导致翻译起始的分子机制尚未被描述。最后，我们评估了mRNA可能通过与18S rRNA碱基配对来招募40S核糖体亚基的可能性。
