Decades of research have yielded significant insight into the mechanism by which a cell translates an mRNA into the encoded protein. However many of the molecular details of the process remain a mystery. Translation initiation is an important control point in gene expression, and misregulation can lead to diseases such as cancer. A better understanding of the mechanism of translation initiation is imperative for the development of novel therapeutic agents. Recently, a combination of genetic, biochemical and biophysical studies has begun to shed light on how, at a molecular level, the translational machinery initiates protein synthesis. In the present review, we briefly compare and contrast the initiation pathways utilized by bacteria, archaea and eukaryotes, and then focus on translation initiation in eukaryotes and recent advances in our understanding of the subunit joining step of the process.

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