From DNA to proteins via the ribosome: Structural insights into the workings of the translation machinery

The translation of the genetic code is one of the most crucial (and energy-costly) processes of life. This task is performed by ribosomes -- large ribonucleoprotein assemblies that read the message encoded in the messenger RNA (mRNA) and synthesise proteins by sequential polymerisation of amino acids carried by transfer RNAs (tRNAs), in the form of aminoacyl-tRNAs (aa-tRNAs). The functional complexity of the protein translation process is reflected by the structural complexity of the ribosome, as it is composed of more than 50 different proteins and several RNA components, even in the simplest organisms. The recent award of the Nobel Prize to three X-ray crystallographers, Venki Ramakrishnan, Tom Steitz and Ada Yonath, amounts to a recognition not only of outstanding individual scientific achievements, but also of the pre-eminent role of this molecular machinery in all forms of life. The architectural sophistication and functional virtuosity of the ribosome are astounding, especially considering that it is one of the most ancient macromolecules, having evidently emerged at the very earliest stages of evolution.The four major steps during protein synthesis by the ribosome are initiation, elongation, termination and recycling (Figure 1). Briefly, in the first step, ribosomal subunits, mRNA and the initiator tRNA (fMet-tRNAfMet) are brought together with the help of initiation factors. Once this initiation complex is formed, the sequential incorporation of aa-tRNAs proceeds based on the cognate match between the codon, a three-base sequence on the mRNA, with the complementary anticodon of the aa-tRNA, a match that is recognised by the decoding centre located on the small subunit. Upon successful selection, the aa-tRNA is accommodated in the ribosome, leading to the immediate transfer of the peptide bond from the peptidyl tRNA to the incoming aa-tRNA. Next, the tRNAs along with the mRNA, are translocated by the span of one codon, and the decoding site is vacated for the