%0 Journal Article
%T Alternative Mechanisms to Initiate Translation in Eukaryotic mRNAs
%A Encarnaci¨®n Mart¨ªnez-Salas
%A David Pi£¿eiro
%A Noem¨ª Fern¨¢ndez
%J International Journal of Genomics
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/391546
%X The composition of the cellular proteome is under the control of multiple processes, one of the most important being translation initiation. The majority of eukaryotic cellular mRNAs initiates translation by the cap-dependent or scanning mode of translation initiation, a mechanism that depends on the recognition of the m7G(5¡ä)ppp(5¡ä)N, known as the cap. However, mRNAs encoding proteins required for cell survival under stress bypass conditions inhibitory to cap-dependent translation; these mRNAs often harbor internal ribosome entry site (IRES) elements in their 5¡äUTRs that mediate internal initiation of translation. This mechanism is also exploited by mRNAs expressed from the genome of viruses infecting eukaryotic cells. In this paper we discuss recent advances in understanding alternative ways to initiate translation across eukaryotic organisms. 1. Alternative Translation Initiation Mechanisms: An Important Layer of Gene Expression Control The coding capacity of eukaryotic genomes is much larger than anticipated. Many layers of gene expression control operate at the posttranscriptional level, as illustrated by the RNA splicing process, the noncoding RNAs regulatory elements, and the large repertoire of factors that contribute to control mRNA transport, localization, stability, and translation. Translation control is one of the posttranscriptional cellular processes that exert a profound impact on the composition of the cellular proteome. This is particularly relevant to maintain homeostasis in response to stress induced by a large variety of environmental factors, as well as during development or disease [1]. In addition, these layers of gene expression control contribute to increase the coding capacity of the genome by generating different polypeptides from the same transcriptional unit. The majority of cellular mRNAs initiate translation by a mechanism that depends on the recognition of the m7G(5¡ä)ppp(5¡ä)N structure (termed cap) located at the 5¡äend of most mRNAs (Figure 1(a)). This manner of initiating translation involves a large number of auxiliary proteins termed eukaryotic initiation factors (eIFs) [1]. The 5¡äcap structure is recognized by eIF4E that, in turn, is bound to the scaffold protein eIF4G and the RNA helicase eIF4A (within a trimeric complex termed eIF4F). Additionally, eIF4G further interacts with eIF3 and the poly(A)-binding protein (PABP) that is bound to the poly(A) tail of the mRNA. Separately, the 40S ribosomal subunit associates with the ternary complex (TC) consisting of the initiator methionyl-tRNAi and eIF2-GTP, leading to the
%U http://www.hindawi.com/journals/ijg/2012/391546/