The cover picture shows a new type of eukaryotic upregulating riboswitch (ON-eRS), engineered by A. Ogawa (see p. 1539 ff.), that activates “ribosomal shunting” in response to a specific ligand. A 40S ribosomal subunit (a green train) that has finished translation at one open reading frame usually looks for the next downstream ORF (dORF, a yellow flag) on mRNA (a black bold line), but some obstacles such as a rigid stem and/or mimic genes (gray rocks on mRNA) prevent the 40S from proceeding (OFF state, left). In contrast, in the presence of a ligand (a round character, ligand-kun) that properly binds to the mRNA, the 40S can shunt over the obstacles to reach the dORF through a bypass formed by the ligand–mRNA interaction (ON state, right). This hybridization switch-free riboswitch has a great advantage in that it saves energy for the regulation of gene expression. The background shows tram rails in Matsuyama, Japan.