70S-scanning initiation is a novel and frequent initiation mode of ribosomal translation in bacteria

Until now, two initiation modes for bacterial translation have been described: (i) the standard 30S-binding mode, where the small ribosomal subunit selects the initiation site on an mRNA with the help of three initiation factors (IFs), and (ii) the rare initiation of leaderless mRNAs, which are mRNAs carrying the initiation AUG within the first 5 nt at the 5'-end. The existence of a third "70S-scanning" mode for bacterial initiation was conjectured in past decades but has remained experimentally unproven. Here, we demonstrate the existence of a 70S-scanning mode of initiation and characterize its mechanistic features. The three initiation modes demonstrate specific patterns of requirements for IF1 and IF3.