[Perspective] IRES unplugged
All cellular messenger RNAs (mRNAs) have a 7-methylguanosine (m7GpppN) cap structure at their 5′ ends, which promotes efficient translation and mRNA stability. The cap is recognized by the translation initiation factor eIF4F. eIF4F recruits the 40S small ribosomal subunit near the mRNA cap, which then scans the 5′ untranslated region (UTR) toward the initiation codon for subsequent protein synthesis. In conditions of stress or during viral infections, cap-dependent translation is compromised. Internal ribosome entry sites (IRESs) can bypass the cap to recruit ribosomes internally to the transcript, helping to secure appropriate protein synthesis under such conditions. On page 240 of this issue, Weingarten-Gabbay et al. (1) report the systematic discovery of cellular and viral IRESs, identifying a substantial fraction of mRNAs (∼10%) and viruses (∼20%) with the potential to be translated by this cap-independent mechanism. Authors: Fátima Gebauer, Matthias W. Hentze