Internal Ribosome Entry Sites Tests with Circular mRNAs

It was shown that eukaryotic ribosomes, in contrast to prokaryotic ribosomes, were unable to bind to small circular RNAs ( 1 , 2 ). This finding was a key feature in the scanning model for translational initiation, which postulates that eukaryotic 40S ribosomal subunits enter mRNAs exclusively at their free, capped 5′ ends like beads on a string ( 3 ). Subsequently, 40S subunits carrying eukaryotic translation initiation factors and initiator tRNAs are thought to scan the mRNA in a 5′ to 3′ direction until an appropriate AUG codon is encountered that can be used as start site for protein biosynthesis ( 3 ). However, this model has been challenged with the discovery of internal ribosome entry site (IRES) elements, present in certain viral and cellular mRNAs, that can mediate translational initiation without prior scanning of the mRNA by 40S sub-units ( 4 – 9 ). These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.